Note: This page contains sample records for the topic basic helix-loop-helix protein-mediated from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

The Basic Helix-Loop-Helix Transcription Factor Family in the Honey Bee, Apis mellifera  

Microsoft Academic Search

The basic helix-loop-helix (bHLH) transcription factors play important roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in a dozen of organisms including fruit fly, mouse and human. In this study, we identified 51 bHLH sequences in silico in the honey bee, Apis mellifera L. (Hymenoptera: Apidae), genome. Phylogenetic analyses revealed that

Yong Wang; Keping Chen; Qin Yao; Wenbing Wang; Zhi Zhu

2008-01-01

2

A triple helix-loop-helix/basic helix-loop-helix cascade controls cell elongation downstream of multiple hormonal and environmental signaling pathways in Arabidopsis.  

PubMed

Environmental and endogenous signals, including light, temperature, brassinosteroid (BR), and gibberellin (GA), regulate cell elongation largely by influencing the expression of the paclobutrazol-resistant (PRE) family helix-loop-helix (HLH) factors, which promote cell elongation by interacting antagonistically with another HLH factor, IBH1. However, the molecular mechanism by which PREs and IBH1 regulate gene expression has remained unknown. Here, we show that IBH1 interacts with and inhibits a DNA binding basic helix-loop-helix (bHLH) protein, HBI1, in Arabidopsis thaliana. Overexpression of HBI1 increased hypocotyl and petiole elongation, whereas dominant inactivation of HBI1 and its homologs caused a dwarf phenotype, indicating that HBI1 is a positive regulator of cell elongation. In vitro and in vivo experiments showed that HBI1 directly bound to the promoters and activated two EXPANSIN genes encoding cell wall-loosening enzymes; HBI1's DNA binding and transcriptional activities were inhibited by IBH1, but the inhibitory effects of IBH1 were abolished by PRE1. The results indicate that PREs activate the DNA binding bHLH factor HBI1 by sequestering its inhibitor IBH1. Altering each of the three factors affected plant sensitivities to BR, GA, temperature, and light. Our study demonstrates that PREs, IBH1, and HBI1 form a chain of antagonistic switches that regulates cell elongation downstream of multiple external and endogenous signals. PMID:23221598

Bai, Ming-Yi; Fan, Min; Oh, Eunkyoo; Wang, Zhi-Yong

2012-12-01

3

A Triple Helix-Loop-Helix/Basic Helix-Loop-Helix Cascade Controls Cell Elongation Downstream of Multiple Hormonal and Environmental Signaling Pathways in Arabidopsis[C][W  

PubMed Central

Environmental and endogenous signals, including light, temperature, brassinosteroid (BR), and gibberellin (GA), regulate cell elongation largely by influencing the expression of the paclobutrazol-resistant (PRE) family helix-loop-helix (HLH) factors, which promote cell elongation by interacting antagonistically with another HLH factor, IBH1. However, the molecular mechanism by which PREs and IBH1 regulate gene expression has remained unknown. Here, we show that IBH1 interacts with and inhibits a DNA binding basic helix-loop-helix (bHLH) protein, HBI1, in Arabidopsis thaliana. Overexpression of HBI1 increased hypocotyl and petiole elongation, whereas dominant inactivation of HBI1 and its homologs caused a dwarf phenotype, indicating that HBI1 is a positive regulator of cell elongation. In vitro and in vivo experiments showed that HBI1 directly bound to the promoters and activated two EXPANSIN genes encoding cell wall–loosening enzymes; HBI1’s DNA binding and transcriptional activities were inhibited by IBH1, but the inhibitory effects of IBH1 were abolished by PRE1. The results indicate that PREs activate the DNA binding bHLH factor HBI1 by sequestering its inhibitor IBH1. Altering each of the three factors affected plant sensitivities to BR, GA, temperature, and light. Our study demonstrates that PREs, IBH1, and HBI1 form a chain of antagonistic switches that regulates cell elongation downstream of multiple external and endogenous signals.

Bai, Ming-Yi; Fan, Min; Oh, Eunkyoo; Wang, Zhi-Yong

2012-01-01

4

Helix-loop-helix/basic helix-loop-helix transcription factor network represses cell elongation in Arabidopsis through an apparent incoherent feed-forward loop.  

PubMed

Cell elongation is promoted by different environmental and hormonal signals, involving light, temperature, brassinosteroid (BR), and gibberellin, that inhibit the atypical basic helix-loop-helix (bHLH) transcription factor INCREASED LEAF INCLINATION1 BINDING bHLH1 (IBH1). Ectopic accumulation of IBH1 causes a severe dwarf phenotype, but the cell elongation suppression mechanism is still not well understood. Here, we identified a close homolog of IBH1, IBH1-LIKE1 (IBL1), that also antagonized BR responses and cell elongation. Genome-wide expression analyses showed that IBH1 and IBL1 act interdependently downstream of the BRASSINAZOLE-RESISTANT1 (BZR1)-PHYTOCHROME-INTERACTING FACTOR 4 (PIF4)-DELLA module. Although characterized as non-DNA binding, IBH1 repressed direct IBL1 transcription, and they both acted in tandem to suppress the expression of a common downstream helix-loop-helix (HLH)/bHLH network, thus forming an incoherent feed-forward loop. IBH1 and IBL1 together repressed the expression of PIF4, known to stimulate skotomorphogenesis synergistically with BZR1. Strikingly, PIF4 bound all direct and down-regulated HLH/bHLH targets of IBH1 and IBL1. Additional genome-wide comparisons suggested a model in which IBH1 antagonized PIF4 but not the PIF4-BZR1 dimer. PMID:24505057

Zhiponova, Miroslava K; Morohashi, Kengo; Vanhoutte, Isabelle; Machemer-Noonan, Katja; Revalska, Miglena; Van Montagu, Marc; Grotewold, Erich; Russinova, Eugenia

2014-02-18

5

The Basic Helix-Loop-Helix Transcription Factor Family in the Honey Bee, Apis mellifera  

PubMed Central

The basic helix-loop-helix (bHLH) transcription factors play important roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in a dozen of organisms including fruit fly, mouse and human. In this study, we identified 51 bHLH sequences in silico in the honey bee, Apis mellifera L. (Hymenoptera: Apidae), genome. Phylogenetic analyses revealed that they belong to 38 bHLH families with 21, 11, 9, 1, 8 and 1 members in high-order groups A, B, C, D, E and F, respectively. Using phylogenetic analyses, all of the 51 bHLH sequences were assigned to their corresponding families. Genes that encode ASCb, NeuroD, Oligo, Delilah, MyoRb, Figa and Mad were not found in the honey bee genome. The present study provides useful background information for future studies using the honey bee as a model system for insect development.

Wang, Yong; Chen, Keping; Yao, Qin; Wang, Wenbing; Zhu, Zhi

2008-01-01

6

A Triantagonistic Basic Helix-Loop-Helix System Regulates Cell Elongation in Arabidopsis[W][OA  

PubMed Central

In plants, basic helix-loop-helix (bHLH) transcription factors play important roles in the control of cell elongation. Two bHLH proteins, PACLOBTRAZOL RESISTANCE1 (PRE1) and Arabidopsis ILI1 binding bHLH1 (IBH1), antagonistically regulate cell elongation in response to brassinosteroid and gibberellin signaling, but the detailed molecular mechanisms by which these factors regulate cell elongation remain unclear. Here, we identify the bHLH transcriptional activators for cell elongation (ACEs) and demonstrate that PRE1, IBH1, and the ACEs constitute a triantagonistic bHLH system that competitively regulates cell elongation. In this system, the ACE bHLH transcription factors directly activate the expression of enzyme genes for cell elongation by interacting with their promoter regions. IBH1 negatively regulates cell elongation by interacting with the ACEs and thus interfering with their DNA binding. PRE1 interacts with IBH1 and counteracts the ability of IBH1 to affect ACEs. Therefore, PRE1 restores the transcriptional activity of ACEs, resulting in induction of cell elongation. The balance of triantagonistic bHLH proteins, ACEs, IBH1, and PRE1, might be important for determination of the size of plant cells. The expression of IBH1 and PRE1 is regulated by brassinosteroid, gibberellins, and developmental phase dependent factors, indicating that two phytohormones and phase-dependent signals are integrated by this triantagonistic bHLH system.

Ikeda, Miho; Fujiwara, Sumire; Mitsuda, Nobutaka; Ohme-Takagi, Masaru

2012-01-01

7

Possible roles of basic helix-loop-helix transcription factors in adaptation to drought.  

PubMed

Water deficiency decreases plant growth and productivity. Several mechanisms are activated in response to dehydration that allows plants to cope with stress, including factors controlling stomatal aperture and ramified root system development. In addition, ABA metabolism is also implicated in the regulation of drought responses. The basic helix-loop-helix (bHLH) proteins, a large family of conserved transcription factors that regulates many cellular processes in eukaryotic organisms, are also involved in several responses that are important for plants to cope with drought stress. This review discusses distinct mechanisms related to drought-adaptive responses, especially the possible involvement of the bHLH transcription factors such as MUTE, implicated in stomatal development; RD29, an ABA-responsive gene; EGL3 and GL3, involved in thichome and root hair development; and SPT, which play roles in repressing leaf expansion. Transcription factors are potential targets for new strategies to increase the tolerance of cultivars to drought stress. Recognition of gene regulatory networks in crops is challenging, and the manipulation of bHLH genes as well as components that mediate bHLH transcription factor responses in different pathways could be essential to achieve abiotic stress tolerance in plants through genetic manipulation. PMID:24767109

Castilhos, Graciela; Lazzarotto, Fernanda; Spagnolo-Fonini, Leila; Bodanese-Zanettini, Maria Helena; Margis-Pinheiro, Márcia

2014-06-01

8

Molecular Cloning and Characterization of DEC2, a New Member of Basic Helix-Loop-Helix Proteins  

Microsoft Academic Search

DEC1 is a basic helix-loop-helix (bHLH) protein related to Drosophila Hairy, Enhancer of split and HES, and involved in the control of proliferation and\\/or differentiation of chondrocytes, neurons, etc. We report here the identification and characterization of human, mouse and rat DEC2, a novel member of the DEC subfamily. DEC2 had high (97%) and moderate (52%) similarities in the bHLH

Katsumi Fujimoto; Ming Shen; Mitsuhide Noshiro; Kazumi Matsubara; Sohei Shingu; Kiyomasa Honda; Eri Yoshida; Ketut Suardita; Yoichi Matsuda; Yukio Kato

2001-01-01

9

The Basic Helix-Loop-Helix Leucine Zipper Transcription Factor Mitf Is Conserved in Drosophila and Functions in Eye Development  

Microsoft Academic Search

The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive

Jon H. Hallsson; Benedikta S. Haflidadottir; Chad Stivers; Ward Odenwald; Heinz Arnheiter; Francesca Pignoni; Eirõ ´ kur Steingrõ ´ msson

2004-01-01

10

The Basic-Helix-Loop-Helix-PAS Orphan MOP3 Forms Transcriptionally Active Complexes with Circadian and Hypoxia Factors  

Microsoft Academic Search

We report that MOP3 is a general dimerization partner for a subset of the basic-helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) superfamily of transcriptional regulators. We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor 1alpha (HIF1alpha ), and HIF2alpha , A DNA selection protocol revealed that the MOP3-MOP4 heterodimer bound a CACGTGA-containing DNA element. Transient transfection experiments demonstrated that the MOP3-MOP4 and MOP3-CLOCK

John B. Hogenesch; Yi-Zhong Gu; Sanjay Jain; Christopher A. Bradfield

1998-01-01

11

Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.  

PubMed Central

Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia. Images Fig. 3 Fig. 4

Wang, G L; Jiang, B H; Rue, E A; Semenza, G L

1995-01-01

12

Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions.  

PubMed

Establishment of long-range fiber tracts by neocortical projection neurons is fundamental for higher brain functions. The molecular control of axon tract formation, however, is still poorly understood. Here, we have identified basic helix-loop-helix (bHLH) transcription factors Neurod2 and Neurod6 as key regulators of fasciculation and targeted axogenesis in the mouse neocortex. In Neurod2/6 double-mutant mice, callosal axons lack expression of the cell adhesion molecule Contactin2, defasciculate in the subventricular zone, and fail to grow toward the midline without forming Probst bundles. Instead, mutant axons overexpress Robo1 and follow random trajectories into the ipsilateral cortex. In contrast to long-range axogenesis, generation and maintenance of pyramidal neurons and initial axon outgrowth are grossly normal, suggesting that these processes are under distinct transcriptional control. Our findings define a new stage in corpus callosum development and demonstrate that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of remote connectivity. PMID:23303943

Bormuth, Ingo; Yan, Kuo; Yonemasu, Tomoko; Gummert, Maike; Zhang, Mingyue; Wichert, Sven; Grishina, Olga; Pieper, Alexander; Zhang, Weiqi; Goebbels, Sandra; Tarabykin, Victor; Nave, Klaus-Armin; Schwab, Markus H

2013-01-01

13

Basic helix-loop-helix transcription factor Tcfl5 interacts with the Calmegin gene promoter in mouse spermatogenesis  

PubMed Central

In mouse spermatogenesis, differentiating germ line cells initiate expression of specific genes at subsequent developmental steps. The Calmegin (Clgn) gene is first expressed in meiotic prophase, in primary spermatocytes, and encodes a protein that acts as a chaperone. To identify testis-specific transcription factors that control expression of the Clgn gene in spermatogenesis, we performed a yeast one-hybrid screening with a Clgn promoter sequence as bait DNA. This screening resulted in the identification of mouse Tcfl5 as a candidate Clgn promoter-binding protein. Tcfl5 is a member of the basic helix–loop–helix (bHLH) family of transcription factors, and mouse Tcfl5 shows 83% amino acid sequence identity with human TCFL5. Gel-shift and yeast one-hybrid experiments showed that Tcfl5 interacts with a non-canonical CACGCG site that is present in the Clgn promoter. By using northern blot, RT–PCR and in situ hybridization, mouse Tcfl5 mRNA was detected only in testis, with the highest expression level in primary spermatocytes and round spermatids. The highest level of Tcfl5 protein was found in primary spermatocytes at the diplotene stage of meiotic prophase, where the protein colocalizes with transcriptionally active chromatin.

Siep, Michel; Sleddens-Linkels, Esther; Mulders, Sabine; van Eenennaam, Hans; Wassenaar, Evelyne; Van Cappellen, Wiggert A.; Hoogerbrugge, Jos; Grootegoed, J. Anton; Baarends, Willy M.

2004-01-01

14

Characterization of ABF-1, a Novel Basic Helix-Loop-Helix Transcription Factor Expressed in Activated B Lymphocytes  

PubMed Central

Proteins of the basic helix-loop-helix (bHLH) family are required for a number of different developmental pathways, including neurogenesis, lymphopoiesis, myogenesis, and sex determination. Using a yeast two-hybrid screen, we have identified a new bHLH transcription factor, ABF-1, from a human B-cell cDNA library. Within the bHLH region, ABF-1 shows a remarkable conservation with other HLH proteins, including tal-1, NeuroD, and paraxis. Its expression pattern is restricted to a subset of lymphoid tissues, Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines, and activated human B cells. ABF-1 is capable of binding an E-box element either as a homodimer or as a heterodimer with E2A. Furthermore, a heterodimeric complex containing ABF-1 and E2A can be detected in EBV-immortalized lymphoblastoid cell lines. ABF-1 contains a transcriptional repression domain and is capable of inhibiting the transactivation capability of E47 in mammalian cells. ABF-1 represents the first example of a B-cell-restricted bHLH protein, and its expression pattern suggests that ABF-1 may play a role in regulating antigen-dependent B-cell differentiation.

Massari, Mark Eben; Rivera, Richard R.; Voland, Joseph R.; Quong, Melanie W; Breit, Timo M.; van Dongen, Jacques J. M.; de Smit, Oncko; Murre, Cornelis

1998-01-01

15

Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites.  

PubMed Central

Basic helix-loop-helix (bHLH) heterodimer protein complexes regulate transcription of genes during the processes of differentiation and development. To study the molecular basis of early mesodermal differentiation, we sought to identify bHLH proteins from cells of mesodermal origin. By using an interaction cloning strategy with a radiolabled recombinant bHLH protein, E12, a clone encoding a potential heterodimer partner was isolated from an endothelial cell library. This gene (bHLH-EC2) is most homologous to Twist but shares similarity within the bHLH domain with TAL1 and other members of this family. bHLH-EC2 is expressed in cultured endothelial cells and in embryonic stem cell, erythroleukemia, and muscle cell lines in a differentiation-dependent manner. In situ hybridization studies of mouse embryos reveal that bHLH-EC2 is expressed throughout the primitive mesoderm as early as 7.5 days postcoitum. Expression then becomes restricted to the paraxial mesoderm and to the dermamyotome of the developing somite. Expression of bHLH-EC2 in cells destined to become myoblasts thus predates expression of myogenic bHLH factors. bHLH-EC2 is expressed in early endothelial and hematopoietic cells in vivo, as shown by RNA studies of embryonic yolk sac and cultured cells derived from yolk sac explants. These findings suggest that bHLH-EC2 plays a role in the development of multiple cell types derived from the primitive mesoderm. Images

Quertermous, E E; Hidai, H; Blanar, M A; Quertermous, T

1994-01-01

16

The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development.  

PubMed Central

The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive RPE cells hyperproliferate, abnormally express the retinal transcriptional regulator Pax6, and form an ectopic neural retina. Here we report the structure of the Mitf gene in Drosophila and demonstrate expression during embryonic development and in the eye-antennal imaginal disc. In vitro, transcriptional regulation by Drosophila Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6) transcription factor. In vivo, targeted expression of wild-type or dominant-negative Drosophila Mitf results in developmental abnormalities reminiscent of Mitf function in mouse eye development. Our results suggest that the Mitf gene is the original member of the Mitf-Tfe subfamily of bHLH-Zip proteins and that its developmental function is at least partially conserved between vertebrates and invertebrates. These findings further support the common origin of the vertebrate and invertebrate eyes.

Hallsson, Jon H; Haflidadottir, Benedikta S; Stivers, Chad; Odenwald, Ward; Arnheiter, Heinz; Pignoni, Francesca; Steingrimsson, Eirikur

2004-01-01

17

Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain  

PubMed Central

In order to elucidate the function of Myc in the maintenance of pluripotency and self-renewal in mouse embryonic stem cells (mESCs), we screened for novel embryonic stem cell (ESC)-specific interactors of Myc by mass spectrometry. Undifferentiated embryonic cell transcription factor 1 (Utf1) was identified in the screen as a putative Myc binding protein in mESCs. We found that Myc and Utf1 directly interact. Utf1 is a chromatin-associated factor required for maintaining pluripotency and self-renewal in mESCs. It can also replace c-myc during induced pluripotent stem cell (iPSC) generation with relatively high efficiency, and shares target genes with Myc in mESCs highlighting a potentially redundant functional role between Myc and Utf1. A large region of Utf1 was found to be necessary for direct interaction with N-Myc, while the basic helix-loop-helix leucine zipper domain of N-Myc is necessary for direct interaction with Utf1.1

Laskowski, Agnieszka I.; Knoepfler, Paul S.

2013-01-01

18

Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain.  

PubMed

In order to elucidate the function of Myc in the maintenance of pluripotency and self-renewal in mouse embryonic stem cells (mESCs), we screened for novel ESC-specific interactors of Myc by mass spectrometry. Undifferentiated embryonic cell transcription factor 1 (Utf1) was identified in the screen as a putative Myc binding protein in mESCs. We found that Myc and Utf1 directly interact. Utf1 is a chromatin-associated factor required for maintaining pluripotency and self-renewal in mESCs. It can also replace c-myc during induced pluripotent stem cell (iPSC) generation with relatively high efficiency, and shares target genes with Myc in mESCs highlighting a potentially redundant functional role between Myc and Utf1. A large region of Utf1 was found to be necessary for direct interaction with N-Myc, while the basic helix-loop-helix leucine zipper domain of N-Myc is necessary for direct interaction with Utf1. PMID:23665319

Laskowski, Agnieszka I; Knoepfler, Paul S

2013-06-14

19

ETS-Mediated Cooperation between Basic Helix-Loop-Helix Motifs of the Immunoglobulin ? Heavy-Chain Gene Enhancer  

PubMed Central

The ?E motifs of the immunoglobulin ? heavy-chain gene enhancer bind ubiquitously expressed proteins of the basic helix-loop-helix (bHLH) family. These elements work together with other, more tissue-restricted elements to produce B-cell-specific enhancer activity by presently undefined combinatorial mechanisms. We found that ?E2 contributed to transcription activation in B cells only when the ?E3 site was intact, providing the first evidence for functional interactions between bHLH proteins. In vitro assays showed that bHLH zipper proteins binding to ?E3 enhanced Ets-1 binding to ?A. One of the consequences of this protein-protein interaction was to facilitate binding of a second bHLH protein, E47, to the ?E2 site, thereby generating a three-protein–DNA complex. Furthermore, transcriptional synergy between bHLH and bHLH zipper factors also required an intermediate ETS protein, which may bridge the transcription activation domains of the bHLH factors. Our observations define an unusual form of cooperation between bHLH and ETS proteins and suggest mechanisms by which tissue-restricted and ubiquitous factors combine to generate tissue-specific enhancer activity.

Dang, Wei; Sun, Xiao-hong; Sen, Ranjan

1998-01-01

20

Dominant alleles of the basic helix-loop-helix transcription factor ATR2 activate stress-responsive genes in Arabidopsis.  

PubMed Central

Members of the R/B basic helix-loop-helix (bHLH) family of plant transcription factors are involved in a variety of growth and differentiation processes. We isolated a dominant mutation in an R/B-related bHLH transcription factor in the course of studying Arabidopsis tryptophan pathway regulation. This mutant, atr2D, displayed increased expression of several tryptophan genes as well as a subset of other stress-responsive genes. The atr2D mutation creates an aspartate to asparagine change at a position that is highly conserved in R/B factors. Substitutions of other residues with uncharged side chains at this position also conferred dominant phenotypes. Moreover, overexpression of mutant atr2D, but not wild-type ATR2, conferred pleiotropic effects, including reduced size, dark pigmentation, and sterility. Therefore, atr2D is likely to be an altered-function allele that identifies a key regulatory site in the R/B factor coding sequence. Double-mutant analysis with atr1D, an overexpression allele of the ATR1 Myb factor previously isolated in tryptophan regulation screens, showed that atr2D and atr1D have additive effects on tryptophan regulation and are likely to act through distinct mechanisms to activate tryptophan genes. The dominant atr mutations thus provide tools for altering tryptophan metabolism in plants.

Smolen, Gromoslaw A; Pawlowski, Laura; Wilensky, Sharon E; Bender, Judith

2002-01-01

21

Dietary conjugated nonadecadienoic acid prevents adult-onset obesity in nescient basic helix-loop-helix 2 knockout mice.  

PubMed

Conjugated linoleic acid (CLA) has been extensively studied during the last two decades with regard to its effects on controlling body composition. As a cognate to CLA, conjugated nonadecadienoic acid (CNA) has been previously reported to reduce body fat more effectively than CLA. However, it is not known whether CNA supplementation can influence adult-onset obesity. Thus, the purpose of this study was to evaluate the effects of dietary CNA on the prevention of adult-onset inactivity-induced obesity using nescient basic helix-loop-helix 2 knockout (N2KO) mice. CNA supplementation at 0.1 w/w% level starting in the preobese state significantly prevented the reduction of voluntary movement and the increase in weight gain in N2KO mice during the experimental period compared to wild-type animals. In both wild-type and N2KO mice, respiratory exchange ratio was significantly reduced by CNA treatment during light and dark cycles, and dietary CNA significantly increased energy expenditure in N2KO mice. Selected gene expression profiles in white adipose tissue, muscle or liver showed a beneficial action of CNA on lipid metabolism and energy expenditure. These findings suggest that CNA could prevent adult-onset obesity by enhancing voluntary activity and energy expenditure in N2KO mice. PMID:22819563

Kim, Jun Ho; Park, Yooheon; Kim, Daeyoung; Good, Deborah J; Park, Yeonhwa

2013-03-01

22

Differentiation of Arabidopsis Guard Cells: Analysis of the Networks Incorporating the Basic Helix-Loop-Helix Transcription Factor, FAMA1[C][W][OA  

PubMed Central

Nearly all extant land plants possess stomata, the epidermal structures that mediate gas exchange between the plant and the environment. The developmental pathways, cell division patterns, and molecules employed in the generation of these structures are simple examples of processes used in many developmental contexts. One specific module is a set of “master regulator” basic helix-loop-helix transcription factors that regulate individual consecutive steps in stomatal development. Here, we profile transcriptional changes in response to inducible expression of Arabidopsis (Arabidopsis thaliana) FAMA, a basic helix-loop-helix protein whose actions during the final stage in stomatal development regulate both cell division and cell fate. Genes identified by microarray and candidate approaches were then further analyzed to test specific hypothesis about the activity of FAMA, the shape of its regulatory network, and to create a new set of stomata-specific or stomata-enriched reporters.

Hachez, Charles; Ohashi-Ito, Kyoko; Dong, Juan; Bergmann, Dominique C.

2011-01-01

23

Abnormal Heart Development and Lung Remodeling in Mice Lacking the Hypoxia-Inducible Factor-Related Basic Helix-Loop-Helix PAS Protein NEPAS  

Microsoft Academic Search

Hypoxia-inducible factors (HIFs) are crucial for oxygen homeostasis during both embryonic development and postnatal life. Here we show that a novel HIF family basic helix-loop-helix (bHLH) PAS (Per-Arnt-Sim) protein, which is expressed predominantly during embryonic and neonatal stages and thereby designated NEPAS (neonatal and embryonic PAS), acts as a negative regulator of HIF-mediated gene expression. NEPAS mRNA is derived from

Toshiharu Yamashita; Osamu Ohneda; Masumi Nagano; Motoyuki Iemitsu; Yuichi Makino; Hirotoshi Tanaka; Takashi Miyauchi; Katsutoshi Goto; Kinuko Ohneda; Yoshiaki Fujii-Kuriyama; Lorenz Poellinger; Masayuki Yamamoto

2008-01-01

24

A critical role for the loop region of the basic helix-loop-helix\\/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription  

Microsoft Academic Search

The carbohydrate response element (ChoRE) is a cis-acting sequence found in the promoters of genes induced transcriptionally by glucose. The ChoRE is composed of two E box-like motifs that are separated by 5 bp and is recognized by two basic helix-loop-helix\\/leucine zipper (bHLH\\/LZ) proteins, ChREBP and Mlx, which heterodimerize to bind DNA. In this study, we demonstrate that two ChREBP\\/Mlx

Lin Ma; Yuk Y. Sham; Kylie J. Walters; Howard C. Towle

2007-01-01

25

The Drosophila dysfusion Basic Helix-Loop-Helix (bHLH)PAS Gene Controls Tracheal Fusion and Levels of the Trachealess bHLHPAS Protein  

Microsoft Academic Search

The development of the mature insect trachea requires a complex series of cellular events, including tracheal cell specification, cell migration, tubule branching, and tubule fusion. Here we describe the identification of the Drosophila melanogaster dysfusion gene, which encodes a novel basic helix-loop-helix (bHLH)-PAS protein conserved between Caenorhabditis elegans, insects, and humans, and controls tracheal fusion events. The Dysfusion protein functions

Lan Jiang; Stephen T. Crews

2003-01-01

26

SREBP-2, a Second Basic-Helix-Loop-Helix-Leucine Zipper Protein that Stimulates Transcription by Binding to a Sterol Regulatory Element  

Microsoft Academic Search

We report the cDNA cloning of SREBP-2, the second member of a family of basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors that recognize sterol regulatory element 1 (SRE-1). SRE-1, a conditional enhancer in the promoters for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A synthase genes, increases transcription in the absence of sterols and is inactivated when sterols accumulate. Human SREBP-2 contains

Xianxin Hua; Chieko Yokoyama; Jian Wu; Michael R. Briggs; Michael S. Brown; Joseph L. Goldstein; Xiaodong Wang

1993-01-01

27

A cellular factor stimulates ligand-dependent release of hsp90 from the basic helix-loop-helix dioxin receptor.  

PubMed Central

In response to dioxin, the nuclear basic helix-loop-helix (bHLH) dioxin receptor forms a complex with the bHLH partner factor Arnt that regulates target gene transcription by binding to dioxin-responsive sequence motifs. Previously, we have demonstrated that the latent form of dioxin receptor present in extracts from untreated cells is stably associated with molecular chaperone protein hsp90, and Arnt is not a component of this complex. Here, we used a coimmunoprecipitation assay to demonstrate that the in vitro-translated dioxin receptor, but not Arnt, is stably associated with hsp90. Although it showed ligand-binding activity, the in vitro-translated dioxin receptor failed to dissociate from hsp90 upon exposure to ligand. Addition of a specific fraction from wild-type hepatoma cells, however, to the in vitro-expressed receptor promoted dioxin-dependent release of hsp90. This stimulatory effect was mediated via the bHLH dimerization and DNA-binding motif of the receptor. Moreover, ligand-dependent release of hsp90 from the receptor was not promoted by fractionated cytosolic extracts from mutant hepatoma cells which are deficient in the function of bHLH dioxin receptor partner factor Arnt. Thus, our results provide a novel model for regulation of bHLH factor activity and suggest that derepression of the dioxin receptor by ligand-induced release of hsp90 may require bHLH-mediated concomitant recruitment of an additional cellular factor, possibly the structurally related bHLH dimerization partner factor Arnt. In support of this model, addition of in vitro-expressed wild-type Arnt, but not a mutated form of Arnt lacking the bHLH motif, promoted release of hsp90 from the dioxin receptor in the presence of dioxin. Images

McGuire, J; Whitelaw, M L; Pongratz, I; Gustafsson, J A; Poellinger, L

1994-01-01

28

Classification and evolutionary analysis of the basic helix-loop-helix gene family in the green anole lizard, Anolis carolinensis.  

PubMed

Helix-loop-helix (bHLH) proteins play essential regulatory roles in a variety of biological processes. These highly conserved proteins form a large transcription factor superfamily, and are commonly identified in large numbers within animal, plant, and fungal genomes. The bHLH domain has been well studied in many animal species, but has not yet been characterized in non-avian reptiles. In this study, we identified 102 putative bHLH genes in the genome of the green anole lizard, Anolis carolinensis. Based on phylogenetic analysis, these genes were classified into 43 families, with 43, 24, 16, 3, 10, and 3 members assigned into groups A, B, C, D, E, and F, respectively, and 3 members categorized as "orphans". Within-group evolutionary relationships inferred from the phylogenetic analysis were consistent with highly conserved patterns observed for introns and additional domains. Results from phylogenetic analysis of the H/E(spl) family suggest that genome and tandem gene duplications have contributed to this family's expansion. Our classification and evolutionary analysis has provided insights into the evolutionary diversification of animal bHLH genes, and should aid future studies on bHLH protein regulation of key growth and developmental processes. PMID:23756994

Liu, Ake; Wang, Yong; Zhang, Debao; Wang, Xuhua; Song, Huifang; Dang, Chunwang; Yao, Qin; Chen, Keping

2013-08-01

29

Identification and characterization of the zebrafish pharyngeal arch-specific enhancer for the basic helix-loop-helix transcription factor Hand2  

PubMed Central

The development of the vertebrate jaw relies on a network of transcription factors that patterns the dorsal-ventral axis of the pharyngeal arches. Recent findings in both mouse and zebrafish illustrate that the basic-helix-loop-helix transcription factor, Hand2, is crucial in this patterning process. While Hand2 has functionally similar roles in these two species, little is known about the regulatory sequences controlling hand2 expression in zebrafish. Using bioinformatics and Tol2-mediated transgenesis, we have generated zebrafish transgenic reporter lines in which either the mouse or zebrafish arch-specific hand2 enhancer direct expression of a fluorescent reporter. We find that both the mouse and zebrafish enhancers drive early reporter expression in a hand2-specific pattern in the ventral pharyngeal arches of zebrafish embryos. These lines provide useful tools to follow ventral arch cells during vertebrate jaw development while also allowing dissection of hand2 transcriptional regulation during this process.

Ikle, Jennifer M.; Artinger, Kristin B.; Clouthier, David E.

2013-01-01

30

The Drosophila dysfusion basic helix-loop-helix (bHLH)-PAS gene controls tracheal fusion and levels of the trachealess bHLH-PAS protein.  

PubMed

The development of the mature insect trachea requires a complex series of cellular events, including tracheal cell specification, cell migration, tubule branching, and tubule fusion. Here we describe the identification of the Drosophila melanogaster dysfusion gene, which encodes a novel basic helix-loop-helix (bHLH)-PAS protein conserved between Caenorhabditis elegans, insects, and humans, and controls tracheal fusion events. The Dysfusion protein functions as a heterodimer with the Tango bHLH-PAS protein in vivo to form a putative DNA-binding complex. The dysfusion gene is expressed in a variety of embryonic cell types, including tracheal-fusion, leading-edge, foregut atrium cells, nervous system, hindgut, and anal pad cells. RNAi experiments indicate that dysfusion is required for dorsal branch, lateral trunk, and ganglionic branch fusion but not for fusion of the dorsal trunk. The escargot gene, which is also expressed in fusion cells and is required for tracheal fusion, precedes dysfusion expression. Analysis of escargot mutants indicates a complex pattern of dysfusion regulation, such that dysfusion expression is dependent on escargot in the dorsal and ganglionic branches but not the dorsal trunk. Early in tracheal development, the Trachealess bHLH-PAS protein is present at uniformly high levels in all tracheal cells, but since the levels of Dysfusion rise in wild-type fusion cells, the levels of Trachealess in fusion cells decline. The downregulation of Trachealess is dependent on dysfusion function. These results suggest the possibility that competitive interactions between basic helix-loop-helix-PAS proteins (Dysfusion, Trachealess, and possibly Similar) may be important for the proper development of the trachea. PMID:12897136

Jiang, Lan; Crews, Stephen T

2003-08-01

31

Expression of the helix-loop-helix protein, Id, during branching morphogenesis in the kidney  

Microsoft Academic Search

Expression of the helix-loop-helix protein, Id, during branching morphogenesis in the kidney. Id, a member of the helix-loop-helix protein family, is an inhibitor of transcriptional activation by basic-helix-loop-helix proteins. In the developing mouse kidney, Id mRNA was observed as early as 12.5 days post-coitum (dpc) specifically in the condensed mesenchyme surrounding the ureteric buds by in situ hybridization. At 14.5

Melinda K Duncan; Tetsuo Shimamura; Kiran Chada

1994-01-01

32

Molecular characterization of cold-responsive basic helix-loop-helix transcription factors MabHLHs that interact with MaICE1 in banana fruit.  

PubMed

Basic helix-loop-helix (bHLH) transcription factors (TFs) are ubiquitously involved in the response of higher plants to various abiotic stresses. However, little is known about bHLH TFs involved in the cold stress response in economically important fruits. Here, five novel full-length bHLH genes, designated as MabHLH1-MabHLH5, were isolated and characterized from banana fruit. Gene expression profiles revealed that MabHLH1/2/4 were induced by cold stress and methyl jasmonate (MeJA) treatment. Transient assays in tobacco BY2 protoplasts showed that MabHLH1/2/4 promoters were activated by cold stress and MeJA treatments. Moreover, protein-protein interaction analysis demonstrated that MabHLH1/2/4 not only physically interacted with each other to form hetero-dimers in the nucleus, but also interacted with an important upstream component of cold signaling MaICE1, with different interaction domains at their N-terminus. These results indicate that banana fruit cold-responsive MabHLHs may form a big protein complex in the nucleus with MaICE1. Taken together, our findings advance our understanding of the possible involvement of bHLH TFs in the regulatory network of ICE-CBF cold signaling pathway. PMID:23955147

Peng, Huan-Huan; Shan, Wei; Kuang, Jian-Fei; Lu, Wang-Jin; Chen, Jian-Ye

2013-11-01

33

Paraxis is a basic helix-loop-helix protein that positively regulates transcription through binding to specific E-box elements.  

PubMed

Members of the Twist subfamily of basic helix-loop-helix transcription factors are important for the specification of mesodermal derivatives during vertebrate embryogenesis. This subfamily includes both transcriptional activators such as scleraxis, Hand2, and Dermo-1 and repressors such as Twist and Hand1. Paraxis is a member of this subfamily, and it has been shown to regulate morphogenetic events during somitogenesis, including the transition of cells from mesenchyme to epithelium and maintaining anterior/posterior polarity. Mice deficient in paraxis exhibit a caudal truncation of the axial skeleton and fusion of the vertebrae. Considering the developmental importance of paraxis, it is important for future studies to understand the molecular basis of its activity. Here we demonstrate that paraxis can function as a transcriptional activator when it forms a heterodimer with E12. Paraxis is able to bind to a set of E-boxes that overlaps with the closely related scleraxis. Paraxis expression precedes that of scleraxis in the region of the somite fated to form the axial skeleton and tendons and is able to direct transcription from an E-box found in the scleraxis promoter. Further, in the absence of paraxis, Pax-1 is no longer expressed in the somites and presomitic mesoderm. These results suggest that paraxis may regulate early events during chondrogenesis by positively directing transcription of sclerotome-specific genes. PMID:15226298

Wilson-Rawls, Jeanne; Rhee, Jerry M; Rawls, Alan

2004-09-01

34

Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.  

PubMed

Craniosynostosis, the premature fusion of the cranial sutures, is a heterogeneous disorder with a prevalence of ?1 in 2,200 (refs. 1,2). A specific genetic etiology can be identified in ?21% of cases, including mutations of TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, and causes Saethre-Chotzen syndrome, typically associated with coronal synostosis. Using exome sequencing, we identified 38 heterozygous TCF12 mutations in 347 samples from unrelated individuals with craniosynostosis. The mutations predominantly occurred in individuals with coronal synostosis and accounted for 32% and 10% of subjects with bilateral and unilateral pathology, respectively. TCF12 encodes one of three class I E proteins that heterodimerize with class II bHLH proteins such as TWIST1. We show that TCF12 and TWIST1 act synergistically in a transactivation assay and that mice doubly heterozygous for loss-of-function mutations in Tcf12 and Twist1 have severe coronal synostosis. Hence, the dosage of TCF12-TWIST1 heterodimers is critical for normal coronal suture development. PMID:23354436

Sharma, Vikram P; Fenwick, Aimée L; Brockop, Mia S; McGowan, Simon J; Goos, Jacqueline A C; Hoogeboom, A Jeannette M; Brady, Angela F; Jeelani, Nu Owase; Lynch, Sally Ann; Mulliken, John B; Murray, Dylan J; Phipps, Julie M; Sweeney, Elizabeth; Tomkins, Susan E; Wilson, Louise C; Bennett, Sophia; Cornall, Richard J; Broxholme, John; Kanapin, Alexander; Johnson, David; Wall, Steven A; van der Spek, Peter J; Mathijssen, Irene M J; Maxson, Robert E; Twigg, Stephen R F; Wilkie, Andrew O M

2013-03-01

35

Involvement of a nuclear-encoded basic helix-loop-helix protein in transcription of the light-responsive promoter of psbD.  

PubMed

In the chloroplast psbD light-responsive promoter (LRP), a highly conserved sequence exists upstream from the bacterial -10/-35 elements. Multiple sequence-specific DNA binding proteins are predicted to bind to the conserved sequence as transcription factors. Using yeast one-hybrid screening of an Arabidopsis cDNA library, a possible DNA binding protein of the psbD LRP upstream sequence was identified. The protein, designated PTF1, is a novel protein of 355 amino acids (estimated molecular weight of 39.6) that contains a basic helix-loop-helix DNA binding motif in the predicted N-terminal region of the mature protein. Transient expression assay of PTF1-GFP fusion protein showed that PTF1 was localized in chloroplasts. Using the modified DNA sequence in the one-hybrid system, the ACC repeat was shown to be essential for PTF1 binding. The rate of psbD LRP mRNA accumulation was reduced in a T-DNA-inserted Arabidopsis ptf1 mutant. Compared with wild-type plants, the mutant had pale green cotyledons and its growth was inhibited under short-day conditions. These results suggest that PTF1 is a trans-acting factor of the psbD LRP. PMID:11161017

Baba, K; Nakano, T; Yamagishi, K; Yoshida, S

2001-02-01

36

Involvement of a Nuclear-Encoded Basic Helix-Loop-Helix Protein in Transcription of the Light-Responsive Promoter of psbD1  

PubMed Central

In the chloroplast psbD light-responsive promoter (LRP), a highly conserved sequence exists upstream from the bacterial ?10/?35 elements. Multiple sequence-specific DNA binding proteins are predicted to bind to the conserved sequence as transcription factors. Using yeast one-hybrid screening of an Arabidopsis cDNA library, a possible DNA binding protein of the psbD LRP upstream sequence was identified. The protein, designated PTF1, is a novel protein of 355 amino acids (estimated molecular weight of 39.6) that contains a basic helix-loop-helix DNA binding motif in the predicted N-terminal region of the mature protein. Transient expression assay of PTF1-GFP fusion protein showed that PTF1 was localized in chloroplasts. Using the modified DNA sequence in the one-hybrid system, the ACC repeat was shown to be essential for PTF1 binding. The rate of psbD LRP mRNA accumulation was reduced in a T-DNA-inserted Arabidopsis ptf1 mutant. Compared with wild-type plants, the mutant had pale green cotyledons and its growth was inhibited under short-day conditions. These results suggest that PTF1 is a trans-acting factor of the psbD LRP.

Baba, Kyoko; Nakano, Takeshi; Yamagishi, Kazutoshi; Yoshida, Shigeo

2001-01-01

37

Preventive effects of conjugated linoleic acid on obesity by improved physical activity in nescient basic helix-loop-helix 2 knockout mice during growth period.  

PubMed

The purpose of this study was to evaluate whether conjugated linoleic acid (CLA) exposure during the developmental period increases voluntary activity, which would influence obesity outcome later in life. The effects of dietary supplementation of 0.5% CLA in a high fat diet were evaluated in nescient basic helix-loop-helix 2 (Nhlh2) knock-out (N2KO) mice, which is a unique animal model representing inactivity-induced obesity in a pre-obese condition. Male wild type and N2KO mice were fed either control or CLA (0.5%) diet for 8 weeks. As expected, control diet fed N2KO animals showed greater body weight with decreased physical activity in the late stage of the experimental period compared with wild type control. Dietary CLA significantly decreased body weight and adipose depots in both wild type and N2KO mice, and the body weights of both genotypes fed CLA were similar during the experimental period. CLA exposure during the developmental period significantly improved the impairment of physical activity in N2KO mice, but the wild type did not show any effect of CLA. In both genotypes, CLA significantly reduced serum triglycerides levels and down-regulated the mRNA expressions of CCAAT/enhancer binding protein ? (C/EBP?) and leptin in white adipose tissue. These findings suggest that early CLA exposure could prevent obesity with improved voluntary physical activity in N2KO mice. PMID:22944770

Kim, Jun Ho; Gilliard, Darla; Good, Deborah J; Park, Yeonhwa

2012-12-01

38

Antagonistic Basic Helix-Loop-Helix/bZIP Transcription Factors Form Transcriptional Modules That Integrate Light and Reactive Oxygen Species Signaling in Arabidopsis[W  

PubMed Central

The critical developmental switch from heterotrophic to autotrophic growth of plants involves light signaling transduction and the production of reactive oxygen species (ROS). ROS function as signaling molecules that regulate multiple developmental processes, including cell death. However, the relationship between light and ROS signaling remains unclear. Here, we identify transcriptional modules composed of the basic helix-loop-helix and bZIP transcription factors PHYTOCHROME-INTERACTING FACTOR1 (PIF1), PIF3, ELONGATED HYPOCOTYL5 (HY5), and HY5 HOMOLOGY (HYH) that bridge light and ROS signaling to regulate cell death and photooxidative response. We show that pif mutants release more singlet oxygen and exhibit more extensive cell death than the wild type during Arabidopsis thaliana deetiolation. Genome-wide expression profiling indicates that PIF1 represses numerous ROS and stress-related genes. Molecular and biochemical analyses reveal that PIF1/PIF3 and HY5/HYH physically interact and coordinately regulate the expression of five ROS-responsive genes by directly binding to their promoters. Furthermore, PIF1/PIF3 and HY5/HYH function antagonistically during the seedling greening process. In addition, phytochromes, cryptochromes, and CONSTITUTIVE PHOTOMORPHOGENIC1 act upstream to regulate ROS signaling. Together, this study reveals that the PIF1/PIF3-HY5/HYH transcriptional modules mediate crosstalk between light and ROS signaling and sheds light on a new mechanism by which plants adapt to the light environments.

Chen, Dongqin; Xu, Gang; Tang, Weijiang; Jing, Yanjun; Ji, Qiang; Fei, Zhangjun; Lin, Rongcheng

2013-01-01

39

PTF1 Is an Organ-Specific and Notch-Independent Basic Helix-Loop-Helix Complex Containing the Mammalian Suppressor of Hairless (RBP-J) or Its Paralogue, RBP-L  

Microsoft Academic Search

PTF1 is a trimeric transcription factor essential to the development of the pancreas and to the maintenance of the differentiated state of the adult exocrine pancreas. It comprises a dimer of P48\\/PTF1a (a pancreas and neural restricted basic helix-loop-helix (bHLH) protein) and a class A bHLH protein, together with a third protein that we show can be either the mammalian

Thomas M. Beres; Toshihiko Masui; Galvin H. Swift; Ling Shi; R. Michael Henke; Raymond J. MacDonald

2006-01-01

40

Low Resolution Structural Models of the Basic Helix-Loop-Helix Leucine Zipper Domain of Upstream Stimulatory Factor 1 and Its Complexes with DNA from Small Angle X-Ray Scattering Data  

Microsoft Academic Search

The upstream stimulatory factor 1 (USF1) belongs to the basic helix-loop-helix leucine zipper (b\\/HLH\\/Z) transcription factor family, recognizing the CACGTG DNA motive as a dimer and playing an important role in the regulation of transcription in a variety of cellular and viral promoters. In this study we investigate the USF1 b\\/HLH\\/Z domain and its complexes with DNA by small angle

Ekaterina P. Lamber; Matthias Wilmanns; Dmitri I. Svergun

2008-01-01

41

Basic Helix-Loop-Helix Transcription Factor Bmsage Is Involved in Regulation of fibroin H-chain Gene via Interaction with SGF1 in Bombyx mori  

PubMed Central

Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix–loop–helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells.

Li, Qiong-Yan; Hu, Wen-Bo; Zhou, Meng-Ting; Nie, Hong-Yi; Zhang, Yin-Xia; Peng, Zhang-Chuan; Zhao, Ping; Xia, Qing-You

2014-01-01

42

MicroRNA-212 Post-Transcriptionally Regulates Oocyte-Specific Basic-Helix-Loop-Helix Transcription Factor, Factor in the Germline Alpha (FIGLA), during Bovine Early Embryogenesis  

PubMed Central

Factor in the germline alpha (FIGLA) is an oocyte-specific basic helix-loop-helix transcription factor essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. Here we report the characterization of bovine FIGLA gene and its regulation during early embryogenesis. Bovine FIGLA mRNA expression is restricted to gonads and is detected in fetal ovaries harvested as early as 90 days of gestation. FIGLA mRNA and protein are abundant in germinal vesicle and metaphase II stage oocytes, as well as in embryos from pronuclear to eight-cell stage but barely detectable at morula and blastocyst stages, suggesting that FIGLA might be a maternal effect gene. Recent studies in zebrafish and mice have highlighted the importance of non-coding small RNAs (microRNAs) as key regulatory molecules targeting maternal mRNAs for degradation during embryonic development. We hypothesized that FIGLA, as a maternal transcript, is regulated by microRNAs during early embryogenesis. Computational predictions identified a potential microRNA recognition element (MRE) for miR-212 in the 3’ UTR of the bovine FIGLA mRNA. Bovine miR-212 is expressed in oocytes and tends to increase in four-cell and eight-cell stage embryos followed by a decline at morula and blastocyst stages. Transient transfection and reporter assays revealed that miR-212 represses the expression of FIGLA in a MRE dependent manner. In addition, ectopic expression of miR-212 mimic in bovine early embryos dramatically reduced the expression of FIGLA protein. Collectively, our results demonstrate that FIGLA is temporally regulated during bovine early embryogenesis and miR-212 is an important negative regulator of FIGLA during the maternal to zygotic transition in bovine embryos.

Tripurani, Swamy K.; Wee, Gabbine; Lee, Kyung-Bon; Smith, George W.; Wang, Lei; JianboYao

2013-01-01

43

The grapevine basic helix-loop-helix (bHLH) transcription factor positively modulates CBF-pathway and confers tolerance to cold-stress in Arabidopsis.  

PubMed

Basic helix-loop-helix (bHLH)-type transcription factors play diverse roles in plant physiological response and stress-adaptive regulation network. Here, we identified one grapevine bHLH transcription factor from a cold-tolerant accession 'Heilongjiang seedling' of Chinese wild Vitis amurensis (VabHLH1) as a transcriptional activator involved in cold stress. We also compared with its counterpart from a cold-sensitive Vitis vinifera cv. Cabernet Sauvignon (VvbHLH1). These two putative proteins are characterized by the presence of the identically conserved regions of 54 amino acid residues of bHLH signature domain, and shared 99.1 % amino acid identity, whereas several stress-related cis-regulatory elements located in both promoter regions differed in types and positions. Expressions of two bHLHs in grapevine leaves were induced by cold stress, but evidently differ between two grapevine genotypes upon cold exposure. Two grapevine bHLH proteins were exclusively localized to the nucleus and exhibited strong transcriptional activation activities in yeast cells. Overexpression of either VabHLH1 or VvbHLH1 transcription factor did not affect the growth and development of transgenic Arabidopsis plants, but enhanced tolerance to cold stress. The improved tolerance in VabHLH1- or VvbHLH1-overexpressing Arabidopsis plants is associated with multiple physiological and biochemical changes that occurred during the time-course cold stress. These most common changes include the evaluated levels of proline, decreased amounts of malondialdehyde and reduced membrane injury as reflected by electrolyte leakage. VabHLH1 and VvbHLH1 displayed overlapping, but not identical, roles in activating the corresponding CBF cold signaling pathway, especially in regulating the expression of CBF3 and RD29A. Our findings demonstrated that two grapevine bHLHs act as positive regulators of the cold stress response, modulating the level of COR gene expression, which in turn confer tolerance to cold stress. PMID:24859977

Xu, Weirong; Zhang, Ningbo; Jiao, Yuntong; Li, Ruimin; Xiao, Dongming; Wang, Zhenping

2014-08-01

44

E1A-mediated inhibition of myogenesis correlates with a direct physical interaction of E1A12S and basic helix-loop-helix proteins.  

PubMed Central

The observation that adenovirus E1A gene products can inhibit differentiation of skeletal myocytes suggested that E1A may interfere with the activity of myogenic basic helix-loop-helix (bHLH) transcription factors. We have examined the ability of E1A to mediate repression of the muscle-specific creatine kinase (MCK) gene. Both the E1A12S and E1A13S products repressed MCK transcription in a concentration-dependent fashion. In contrast, amino-terminal deletion mutants (d2-36 and d15-35) of E1A12S were defective for repression. E1A12S also repressed expression of a promoter containing a multimer of the MCK high-affinity E box (the consensus site for myogenic bHLH protein binding) that was dependent, in C3H10T1/2 cells, on coexpression of a myogenin bHLH-VP16 fusion protein. A series of coprecipitation experiments with glutathione S-transferase fusion and in vitro-translated proteins demonstrated that E1A12S, but not amino-terminal E1A deletion mutants, could bind to full-length myogenin and E12 and to deletion mutants of myogenin and E12 that spare the bHLH domains. Thus, the bHLH domains of myogenin and E12, and the high-affinity E box, are targets for E1A-mediated repression of the MCK enhancer, and domains of E1A required for repression of muscle-specific gene transcription also mediate binding to bHLH proteins. We conclude that E1A mediates repression of muscle-specific gene transcription through its amino-terminal domain and propose that this may involve a direct physical interaction between E1A and the bHLH region of myogenic determination proteins. Images

Taylor, D A; Kraus, V B; Schwarz, J J; Olson, E N; Kraus, W E

1993-01-01

45

Multiple Roles of Ligand in Transforming the Dioxin Receptor to an Active Basic Helix-Loop-Helix/PAS Transcription Factor Complex with the Nuclear Protein Arnt  

PubMed Central

The dioxin receptor is a ligand-activated transcription factor belonging to an emerging class of basic helix-loop-helix/PAS proteins which show interaction with the molecular chaperone hsp90 in their latent states and require heterodimerization with a general cofactor, Arnt, to form active DNA binding complexes. Upon binding of polycyclic aromatic hydrocarbons typified by dioxin, the dioxin receptor translocates from the cytoplasm to the nucleus to allow interaction with Arnt. Here we have bypassed the nuclear translocation step by creating a cell line which expresses a constitutively nuclear dioxin receptor, which we find remains in a latent form, demonstrating that ligand has functional roles beyond initiating nuclear import of the receptor. Treatment of the nuclear receptor with dioxin induces dimerization with Arnt to form an active transcription factor complex, while in stark contrast, treatment with the hsp90 ligand geldanamycin results in rapid degradation of the receptor. Inhibition of degradation by a proteasome inhibitor allowed geldanamycin to transform the nuclear dioxin receptor to a heterodimer with Arnt (DR-Arnt). Our results indicate that unchaperoned dioxin receptor is extremely labile and is consistent with a concerted nuclear mechanism for receptor activation whereby hsp90 is released from the ligand-bound dioxin receptor concomitant with Arnt dimerization. Strikingly, artificial transformation of the receptor by geldanamycin provided a DR-Arnt complex capable of binding DNA but incapable of stimulating transcription. Limited proteolysis of DR-Arnt heterodimers indicated different conformations for dioxin versus geldanamycin-transformed receptors. Our studies of intracellular dioxin receptor transformation indicate that ligand plays multiple mechanistic roles during receptor activation, being important for nuclear translocation, transformation to an Arnt heterodimer, and maintenance of a structural integrity key for transcriptional activation.

Lees, Michael J.; Whitelaw, Murray L.

1999-01-01

46

Basic Helix-Loop-Helix Transcription Factor Bmsage Is Involved in Regulation of fibroin H-chain Gene via Interaction with SGF1 in Bombyx mori.  

PubMed

Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells. PMID:24740008

Zhao, Xiao-Ming; Liu, Chun; Li, Qiong-Yan; Hu, Wen-Bo; Zhou, Meng-Ting; Nie, Hong-Yi; Zhang, Yin-Xia; Peng, Zhang-Chuan; Zhao, Ping; Xia, Qing-You

2014-01-01

47

Functional Diversity of Human Basic Helix-Loop-Helix Transcription Factor TCF4 Isoforms Generated by Alternative 5? Exon Usage and Splicing  

PubMed Central

Background Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2) is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG). While involved in the development and functioning of many different cell types, recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and TCF4 haploinsufficiency is the cause of the Pitt-Hopkins mental retardation syndrome. However, the structure, expression and coding potential of the human TCF4 gene have not been described in detail. Principal Findings In the present study we used human tissue samples to characterize human TCF4 gene structure and TCF4 expression at mRNA and protein level. We report that although widely expressed, human TCF4 mRNA expression is particularly high in the brain. We demonstrate that usage of numerous 5? exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. For functional characterization of TCF4 isoforms, we overexpressed individual isoforms in cultured human cells. Our analysis revealed that subcellular distribution of TCF4 isoforms is differentially regulated: Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. Furthermore, the ability of different TCF4 isoforms to regulate E-box controlled reporter gene transcription is varied depending on whether one or both of the two TCF4 transcription activation domains are present in the protein. Both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination. Conclusions Altogether, in this study we have described the inter-tissue variability of TCF4 expression in human and provided evidence about the functional diversity of the alternative TCF4 protein isoforms.

Sepp, Mari; Kannike, Kaja; Eesmaa, Ave; Urb, Mari; Timmusk, Tonis

2011-01-01

48

A basic helix-loop-helix transcription factor, PtrbHLH, of Poncirus trifoliata confers cold tolerance and modulates peroxidase-mediated scavenging of hydrogen peroxide.  

PubMed

The basic helix-loop-helix (bHLH) transcription factors are involved in a variety of physiological processes. However, plant bHLHs functioning in cold tolerance and the underlying mechanisms remain poorly understood. Here, we report the identification and functional characterization of PtrbHLH isolated from trifoliate orange (Poncirus trifoliata). The transcript levels of PtrbHLH were up-regulated under various abiotic stresses, particularly cold. PtrbHLH was localized in the nucleus with transactivation activity. Overexpression of PtrbHLH in tobacco (Nicotiana tabacum) or lemon (Citrus limon) conferred enhanced tolerance to cold under chilling or freezing temperatures, whereas down-regulation of PtrbHLH in trifoliate orange by RNA interference (RNAi) resulted in elevated cold sensitivity. A range of stress-responsive genes was up-regulated or down-regulated in the transgenic lemon. Of special note, several peroxidase (POD) genes were induced after cold treatment. Compared with the wild type, POD activity was increased in the overexpression plants but decreased in the RNAi plants, which was inversely correlated with the hydrogen peroxide (H2O2) levels in the tested lines. Treatment of the transgenic tobacco plants with POD inhibitors elevated the H2O2 levels and greatly compromised their cold tolerance, while exogenous replenishment of POD enhanced cold tolerance of the RNAi line. In addition, transgenic tobacco and lemon plants were more tolerant to oxidative stresses. Yeast one-hybrid assay and transient expression analysis demonstrated that PtrbHLH could bind to the E-box elements in the promoter region of a POD gene. Taken together, these results demonstrate that PtrbHLH plays an important role in cold tolerance, at least in part, by positively regulating POD-mediated reactive oxygen species removal. PMID:23624854

Huang, Xiao-San; Wang, Wei; Zhang, Qian; Liu, Ji-Hong

2013-06-01

49

Basic Helix-Loop-Helix Transcription Factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 Are Negative Regulators of Jasmonate Responses in Arabidopsis1[W][OPEN  

PubMed Central

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2.

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-01-01

50

The Basic Helix-Loop-Helix Transcription Factor MYC2 Directly Represses PLETHORA Expression during Jasmonate-Mediated Modulation of the Root Stem Cell Niche in Arabidopsis[W][OA  

PubMed Central

The root stem cell niche, which in the Arabidopsis thaliana root meristem is an area of four mitotically inactive quiescent cells (QCs) and the surrounding mitotically active stem cells, is critical for root development and growth. We report here that during jasmonate-induced inhibition of primary root growth, jasmonate reduces root meristem activity and leads to irregular QC division and columella stem cell differentiation. Consistently, jasmonate reduces the expression levels of the AP2-domain transcription factors PLETHORA1 (PLT1) and PLT2, which form a developmentally instructive protein gradient and mediate auxin-induced regulation of stem cell niche maintenance. Not surprisingly, the effects of jasmonate on root stem cell niche maintenance and PLT expression require the functioning of MYC2/JASMONATE INSENSITIVE1, a basic helix-loop-helix transcription factor that involves versatile aspects of jasmonate-regulated gene expression. Gel shift and chromatin immunoprecipitation experiments reveal that MYC2 directly binds the promoters of PLT1 and PLT2 and represses their expression. We propose that MYC2-mediated repression of PLT expression integrates jasmonate action into the auxin pathway in regulating root meristem activity and stem cell niche maintenance. This study illustrates a molecular framework for jasmonate-induced inhibition of root growth through interaction with the growth regulator auxin.

Chen, Qian; Sun, Jiaqiang; Zhai, Qingzhe; Zhou, Wenkun; Qi, Linlin; Xu, Li; Wang, Bao; Chen, Rong; Jiang, Hongling; Qi, Jing; Li, Xugang; Palme, Klaus; Li, Chuanyou

2011-01-01

51

A Basic Helix-Loop-Helix Transcription Factor, PtrbHLH, of Poncirus trifoliata Confers Cold Tolerance and Modulates Peroxidase-Mediated Scavenging of Hydrogen Peroxide1[C][W  

PubMed Central

The basic helix-loop-helix (bHLH) transcription factors are involved in a variety of physiological processes. However, plant bHLHs functioning in cold tolerance and the underlying mechanisms remain poorly understood. Here, we report the identification and functional characterization of PtrbHLH isolated from trifoliate orange (Poncirus trifoliata). The transcript levels of PtrbHLH were up-regulated under various abiotic stresses, particularly cold. PtrbHLH was localized in the nucleus with transactivation activity. Overexpression of PtrbHLH in tobacco (Nicotiana tabacum) or lemon (Citrus limon) conferred enhanced tolerance to cold under chilling or freezing temperatures, whereas down-regulation of PtrbHLH in trifoliate orange by RNA interference (RNAi) resulted in elevated cold sensitivity. A range of stress-responsive genes was up-regulated or down-regulated in the transgenic lemon. Of special note, several peroxidase (POD) genes were induced after cold treatment. Compared with the wild type, POD activity was increased in the overexpression plants but decreased in the RNAi plants, which was inversely correlated with the hydrogen peroxide (H2O2) levels in the tested lines. Treatment of the transgenic tobacco plants with POD inhibitors elevated the H2O2 levels and greatly compromised their cold tolerance, while exogenous replenishment of POD enhanced cold tolerance of the RNAi line. In addition, transgenic tobacco and lemon plants were more tolerant to oxidative stresses. Yeast one-hybrid assay and transient expression analysis demonstrated that PtrbHLH could bind to the E-box elements in the promoter region of a POD gene. Taken together, these results demonstrate that PtrbHLH plays an important role in cold tolerance, at least in part, by positively regulating POD-mediated reactive oxygen species removal.

Huang, Xiao-San; Wang, Wei; Zhang, Qian; Liu, Ji-Hong

2013-01-01

52

FoSTUA, encoding a basic helix-loop-helix protein, differentially regulates development of three kinds of asexual spores, macroconidia, microconidia, and chlamydospores, in the fungal plant pathogen Fusarium oxysporum.  

PubMed

The soil-borne fungus Fusarium oxysporum causes vascular wilt of a wide variety of plant species. F. oxysporum produces three kinds of asexual spores, macroconidia, microconidia, and chlamydospores. Falcate macroconidia are formed generally from terminal phialides on conidiophores and rarely from intercalary phialides on hyphae. Ellipsoidal microconidia are formed from intercalary phialides on hyphae. Globose chlamydospores with thick walls are developed by the modification of hyphal and conidial cells. Here we describe FoSTUA of F. oxysporum, which differentially regulates the development of macroconidia, microconidia, and chlamydospores. FoSTUA encodes a basic helix-loop-helix protein with similarity to Aspergillus nidulans StuA, which has been identified as a transcriptional regulator controlling conidiation. Nuclear localization of FoStuA was verified by using strains expressing FoStuA-green fluorescent protein fusions. The FoSTUA-targeted mutants exhibited normal microconidium formation in cultures. However, the mutants lacked conidiophores and produced macroconidia at low frequencies only from intercalary phialides. Thus, FoSTUA appears to be necessary to induce conidiophore differentiation. In contrast, chlamydospore formation was dramatically promoted in the mutants. These data demonstrate that FoStuA is a positive regulator and a negative regulator for the development of macroconidia and chlamydospores, respectively, and is dispensable for microconidium formation in cultures. The disease-causing ability of F. oxysporum was not affected by mutations in FoSTUA. However, the mutants produced markedly fewer macroconidia and microconidia in infected plants than the wild type. These results suggest that FoSTUA also has an important role for microconidium formation specifically in infected plants. PMID:15590816

Ohara, Toshiaki; Tsuge, Takashi

2004-12-01

53

The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone  

SciTech Connect

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

2012-10-15

54

Regulation of Id1 and Its Association with Basic Helix-Loop- Helix Proteins during Nerve Growth Factor-Induced Differentiation of PC12 Cells  

Microsoft Academic Search

Cell differentiation in the nervous system is dictated by specific patterns of gene expression. We have investigatedtheroleofhelix-loop-helix(HLH)proteinsduringdifferentiationofPC12pheochromocytomacells in response to nerve growth factor. Gel mobility shift assays using PC12 cell nuclear extracts demonstrated that active basic HLH complexes exist throughout differentiation. Addition of exogeneous Id1 protein, a negative regulator of basic HLH proteins, disrupted specific complexes formed by PC12 cell

MARGRET B. EINARSON; ANDMOSES V. CHAO

1995-01-01

55

A Cysteine Residue in the Helix-Loop-Helix Domain of Id2 Is Critical for Homodimerization and Function  

Microsoft Academic Search

Id proteins are negative regulators of basic helix-loop-helix (bHLH) transcription factors. In this study, we compared the expression of Id2 mRNA in proliferating (fetal) and nonproliferating (adult) alveolar epithelial cells (AECs). The expression of Id2 was higher in adult AECs than in the corresponding fetal cells, suggesting that Id2 might play a functional role in developmental regulation of lung epithelial

Jian Liu; Wei Shi; David Warburton

2000-01-01

56

Molecular Cloning of ID4, a Novel Dominant Negative Helix-Loop-Helix Human Gene on Chromosome 6p21.3-p22  

Microsoft Academic Search

Transcription factors containing a basic helix-loop-helix (bHLH) motif regulate the expression of tissue-specific genes in a number of mammalian and insect systems. DNA-binding activity of the bHLH proteins is dependent upon formation of homo- and\\/or heterodimers. Dominant negative HLH proteins (Id-related genes) also contain the HLH-dimerization domain but lack the DNA-binding basic domain. Consequently, Id proteins inhibit binding to DNA

Alfredo Pagliuca; Paola Cannada Bartoli; Salvatore Saccone; Giuliano Della Valle; Luigi Lania

1995-01-01

57

The helix-loop-helix transcription factor TWIST is dysregulated in myelodysplastic syndromes  

PubMed Central

Patients with low-grade myelodysplastic syndromes (MDS) show high levels of tumor necrosis factor ? (TNF?) and up-regulation of apoptosis in the marrow. In contrast, marrow cells in advanced MDS are typically resistant to TNF?-induced apoptosis but are rendered apoptosis-sensitive on coculture with stroma. The present studies show that CD34+ marrow cells in advanced MDS express high levels of TWIST, a basic helix-loop-helix transcription factor that opposes p53 function. TWIST levels correlated with disease stage (advanced > low grade; P = .01). Coculture with HS5 stroma resulted in down-regulation of TWIST and increased apoptosis in response to TNF? in CD34+ cells from advanced MDS; the same effect was achieved by TWIST-specific RNA interference in CD34+ cells. In primary MDS marrow stroma TWIST expression was lower than in healthy controls; suppression of TWIST in stroma interfered with induction of apoptosis sensitivity in cocultured CD34+ cells. Stroma cells so modified expressed reduced levels of intercellular adhesion molecule-1 (ICAM1; CD54); blockade of ICAM1 in unmodified stroma was associated with reduced apoptosis in cocultured CD34+ MDS marrow cells. These data suggest role for dysregulation of TWIST in the pathophysiology of MDS. Conceivably, TWIST or components in the signaling pathway could serve as therapeutic targets for patients with MDS.

Li, Xiang; Marcondes, A. Mario; Gooley, Theodore A.

2010-01-01

58

Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins.  

PubMed Central

Tumor-specific activation of the TAL1 gene is the most common genetic alteration seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA-binding motif common to several known transcription factors. A binding-site selection procedure has now been used to evaluate the DNA recognition properties of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic DNA-binding activity, presumably because of their inability to form bHLH homodimers. However, TAL1 readily interacts with any of the known class A bHLH proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset of E-box elements (CANNTG) that can be represented by the consensus sequence AACAGATGGT. This consensus is composed of half-sites for recognition by the participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT). TAL1 heterodimers with DNA-binding activity are readily detected in nuclear extracts of Jurkat, a leukemic cell line derived from a patient with T-cell acute lymphoblastic leukemia. Hence, TAL1 is likely to bind and regulate the transcription of a unique subset of subordinate target genes, some of which may mediate the malignant function of TAL1 during T-cell leukemogenesis. Images

Hsu, H L; Huang, L; Tsan, J T; Funk, W; Wright, W E; Hu, J S; Kingston, R E; Baer, R

1994-01-01

59

Self-recognition behavior of a helix-loop-helix domain by a fragment scan.  

PubMed

The inhibitors of DNA binding Id1-4 are helix-loop-helix (HLH) proteins that exert their biological function by interacting with members of the basic-HLH (bHLH) transcription-factor family. The HLH domains of the Id and bHLH proteins allow both self- and hetero-association. Due to their abnormal expression in cancer cells, the Id proteins are potential protein targets for cancer treatment. Suitable Id-protein inactivators should promote self-association and/or prevent hetero-association. In this work we evaluated the ability of the Id-protein HLH domain to recognize itself in form of short sequences extracted from the helical and loop regions. We performed a peptide scan of the Id1 HLH domain 64-106 based on three-residue overlapping octapeptides. Interaction of each octapeptide with the natively folded Id1 HLH domain was investigated by CD and fluorescence spectroscopy. The results from both techniques showed that the helix-based but not the loop-based octapeptides interacted with the Id1 HLH domain in the low-micromolar range. In contrast, a nitrotyrosine-containing analog of the Id1 HLH region, which was unable to reproduce the native-like conformation, quenched only the 2-amino-benzoyl-(Abz)-labeled loop-based octapeptides. This opposite self-recognition pattern suggests that the short helix-based and loop-based sequences should be able to distinguish different folding states of the Id1 HLH domain. This feature may be biologically relevant, as the Id proteins are predicted to behave as intrinsically disordered proteins, being in equilibrium between rapidly exchanging monomeric conformations and structurally better-defined homo-/heterodimers displaying the parallel four-helix bundle. PMID:24981796

Beisswenger, Michael; Cabrele, Chiara

2014-09-01

60

Id Helix-Loop-Helix Proteins Antagonize Pax Transcription Factor Activity by Inhibiting DNA Binding  

Microsoft Academic Search

The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation of cellular proliferation and differentiation. The major mechanism by which Id proteins are thought to inhibit differen- tiation is through interaction with other HLH proteins and inhibition of their DNA-binding activity. However, Id proteins have also been shown to interact with other proteins involved in regulating

E. CLAIRE ROBERTS; RICHARD W. DEED; TOSHIAKI INOUE; JOHN D. NORTON; ANDREW D. SHARROCKS

2001-01-01

61

Melanocortin 4 receptor is a transcriptional target of nescient helix-loop-helix-2  

Microsoft Academic Search

Melanocortin 4 receptor (Mc4r\\/MC4R) is a G-Protein coupled receptor that is expressed in the hypothalamus and implicated in body weight control. Mutations in MC4R are the most frequent cause of monogenetic forms of human obesity. Despite its importance, the MC4R signaling pathways and transcriptional regulation underlying the melanocortin pathway are far from being fully understood. The transcription factor nescient helix-loop-helix

Umesh D. Wankhade; Deborah J. Good

2011-01-01

62

Characterization of a helix-loop-helix (EF hand) motif of silver hake parvalbumin isoform B.  

PubMed Central

Parvalbumins are a class of calcium-binding proteins characterized by the presence of several helix-loop-helix (EF-hand) motifs. It is suspected that these proteins evolved via intragene duplication from a single EF-hand. Silver hake parvalbumin (SHPV) consists of three EF-type helix-loop-helix regions, two of which have the ability to bind calcium. The three helix-loop-helix motifs are designated AB, CD, and EF, respectively. In this study, native silver hake parvalbumin isoform B (SHPV-B) has been sequenced by mass spectrometry. The sequence indicates that this parvalbumin is a beta-lineage parvalbumin. SHPV-B was cleaved into two major fragments, consisting of the ABCD and EF regions of the native protein. The 33-amino acid EF fragment (residues 76-108), containing one of the calcium ion binding sites in native SHPV-B, has been isolated and studied for its structural characteristics, ability to bind divalent and trivalent cations, and for its propensity to undergo metal ion-induced self-association. The presence of Ca2+ does not induce significant secondary structure in the EF fragment. However, NMR and CD results indicate significant secondary structure promotion in the EF fragment in the presence of the higher charge-density trivalent cations. Sedimentation equilibrium analysis results show that the EF fragment exists in a monomer-dimer equilibrium when complexed with La3+.

Revett, S. P.; King, G.; Shabanowitz, J.; Hunt, D. F.; Hartman, K. L.; Laue, T. M.; Nelson, D. J.

1997-01-01

63

Helix-loop-helix-type transcription factor (HES-1) is expressed in osteoblastic cells, suppressed by 1,25(OH) 2 vitamin D 3, and modulates 1,25(OH) 2 vitamin D 3 enhancement of osteopontin gene expression  

Microsoft Academic Search

The active form of vitamin D, 1,25(OH)2 vitamin D3 (D3), is a potent modulator of osteoblastic function. In this study, we examined, the expression of a negative-type basic helix-loop-helix transcription factor, HES-1, in osteoblastic cells and the regulation of its expression by D3. We found that HES-1 is expressed as a 1.7 kb mRNA in rat osteoblastic osteosarcoma ROS17\\/2.8 cells.

M. Matsue; R. Kageyama; D. T. Denhardt; M. Noda

1997-01-01

64

CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human chromosome 10 and mouse chromosome 19  

SciTech Connect

Helix-loop-helix proteins contain stretches of DNA that encode two amphipathic {alpha}-helices joined by a loop structure and are involved in protein dimerization and transcriptional regulation essential to a variety of cellular processes. CHUK, a newly described conserved helix-loop-helix ubiquitous kinase, was mapped by somatic cell hybrid analyses to human Chr 10q24-q25. Chuk and a related sequence, Chuk-rs1, were mapped to mouse chromosomes 19 and 16, respectively, by a combination of somatic cell hybrid, recombinant inbred, and backcross analyses. 17 refs., 2 figs., 1 tab.

Mock, B.A.; McBride, O.W.; Kozak, C.A. [National Institutes of Health, Bethesda, MD (United States)] [and others] [National Institutes of Health, Bethesda, MD (United States); and others

1995-05-20

65

Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47.  

PubMed

The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection. PMID:10587351

Bain, G; Quong, M W; Soloff, R S; Hedrick, S M; Murre, C

1999-12-01

66

Two Single Nucleotide Polymorphisms in the Human Nescient Helix Loop Helix 2 (NHLH2) Gene Reduce mRNA Stability and DNA Binding  

PubMed Central

Nescient Helix Loop Helix-2 (NHLH2) is a basic helix-loop-helix transcription factor, which has been implicated, using mouse knockouts, in adult body weight regulation and fertility. A scan of the known single nucleotide polymorphisms (SNPs) in the NHLH2 gene revealed one in the 3’ untranslated region (3’UTR), which lies within an AUUUA RNA stability motif. A second SNP is nonsynonymous within the coding region of NHLH2, and was found in a genome-wide association study for obesity. Both of these SNPs were examined for their effect on NLHL2 by creating mouse mimics and examining mRNA stability, and protein function in mouse hypothalamic cell lines. The 3’UTR SNP causes increased instability and, when the SNP-containing Nhlh2 3’UTR is attached to luciferase mRNA, reduced protein levels in cells. The nonsynonymous SNP at position 83 in the protein changes an alanine residue, conserved in NHLH2 orthologs through to Drosphilia sp. to a proline residue. This change affects migration of the protein on an SDS-PAGE gel, and appears to alter secondary structure of the protein, as predicted using in silico methods. These results provide functional information on two rare human SNPs in the NHLH2 gene. One of these has been linked to human obese phenotypes, while the other is present in a relatively high proportion of individuals. Given their effects on NHLH2 protein levels, both SNPs deserve further analysis in whether they are causative and/or additive for human body weight and fertility phenotypes.

AL_Rayyan, Numan; Wankhade, Umesh; Bush, Korie; Good, Deborah J.

2012-01-01

67

BuD, a helix-loop-helix DNA-binding domain for genome modification.  

PubMed

DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific protein-DNA interactions in protein scaffolds is key to providing `toolkits' for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19?bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helix-loop-helix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin ? (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing. PMID:25004980

Stella, Stefano; Molina, Rafael; López-Méndez, Blanca; Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza; Campos-Olivas, Ramon; Duchateau, Phillippe; Montoya, Guillermo

2014-07-01

68

BuD, a helix-loop-helix DNA-binding domain for genome modification  

PubMed Central

DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific protein–DNA interactions in protein scaffolds is key to providing ‘toolkits’ for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19?bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helix–loop–helix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin ? (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing.

Stella, Stefano; Molina, Rafael; Lopez-Mendez, Blanca; Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza; Campos-Olivas, Ramon; Duchateau, Phillippe; Montoya, Guillermo

2014-01-01

69

The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.  

PubMed Central

We have analyzed t(1;14)(p32;q11) chromosome translocations from two patients with T cell acute lymphocytic leukemia. The chromosome 1 breakpoints of these patients lie within a kilobasepair of each other, and thus define a genetic locus (designated tal) involved in T cell oncogenesis. Moreover, we have identified sequences within tal that potentially encode an amphipathic helix-loop-helix motif, a DNA-binding domain found in a variety of proteins that control cell growth and differentiation. The homology domain of tal is especially related to that of lyl-1, a gene on chromosome 19 that has also been implicated in T cell oncogenesis. Hence, tal and lyl-1 encode a distinct family of helix-loop-helix proteins involved in the malignant development of lymphocytes. Images Fig. 1. Fig. 3. Fig. 6.

Chen, Q; Cheng, J T; Tasi, L H; Schneider, N; Buchanan, G; Carroll, A; Crist, W; Ozanne, B; Siciliano, M J; Baer, R

1990-01-01

70

A human Id-like helix-loop-helix protein expressed during early development.  

PubMed Central

The interaction of helix-loop-helix (HLH) proteins is known to regulate the differentiation of several different tissues, including mammalian muscle and the insect peripheral nervous system. In myoblasts, the products of myogenic HLH genes such as MyoD and ubiquitous HLH proteins such as E12 are present at constant levels throughout development. An E12 monomer and a MyoD monomer form a DNA binding heterodimer that activates muscle-specific genes. These two proteins are unable to dimerize in proliferating myoblasts because a negative regulator HLH protein, Id, is present. We now report the sequence and structure of a human HLH gene related to Id, which has been designated Id-2. Two prominent Id-2 RNA molecules of 2.5 and 1.3 kilobases were found in a number of different human normal and neoplastic tissues. We believe the larger RNA is a precursor of the 1.3-kilobase mRNA that encodes an Id-2 protein of 134 amino acids. The HLH region of the Id-2 protein is 90% homologous to that of myogenic Id, but the homology is much less extensive outside the HLH region. The Id-2 gene is highly expressed during early fetal development in several tissues, including those of the central nervous system, but is not expressed in the corresponding mature tissues. Id-2 expression is modulated in association with retinoic acid-induced ganglionic differentiation of the neuroblastoma cell line SMS-KCNR. These findings suggest that Id-2 is an inhibitor of tissue-specific gene expression, although its distinctive pattern of expression during development suggests a role different from that of Id. Images

Biggs, J; Murphy, E V; Israel, M A

1992-01-01

71

Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22  

SciTech Connect

Transcription factors containing a basic helix-loop-helix (bHLH) motif regulate the expression of tissue-specific genes in a number of mammalian and insect systems. DNA-binding activity of the bHLH proteins is dependent upon formation of homo- and/or heterodimers. Dominant negative HLH proteins (Id-related genes) also contain the HLH-dimerization domain but lack the DNA-binding basic domain. Consequently, Id proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins. The authors report here the cDNA sequence of a novel human HLH gene (HGMW-approved symbol ID4) that lacks the basic domain. ID4 is differentially expressed in adult organs in four mRNA molecules, which are presumably a result of differential splicing and/or alternative usage of the polyadenylation sites. Transfection experiments indicated that enforced expression of Id-4H protein inhibits the trans-activation of the muscle creatine kinase E-box enhancer by MyoD. Finally, the authors localized the ID4 gene to the chromosome 6p21-p22 region. 18 refs., 4 figs.

Pagliuca, A.; Bartoli, P.C.; Saccone, S. [Universita Federico II, Naples (Italy)] [and others] [Universita Federico II, Naples (Italy); and others

1995-05-01

72

Cloning and sequence analysis of TFE, a helix-loop-helix transcription factor able to recognize the thyroglobulin gene promoter in vitro.  

PubMed Central

A cDNA that encodes a transcription factor able to recognize the thyroglobulin gene promoter in vitro was isolated from a dog thyroid cDNA expression library in lambda gt11. The library was screened with a multimerized 20 bp-oligonucleotide probe corresponding to the -126 to -107 bp region of the bovine thyroglobulin gene promoter. The specificity of DNA sequence recognition was demonstrated by DNA binding experiments realized with beta-galactosidase-fusion protein immobilized on nitrocellulose filters and various unlabelled multimerized competing DNA fragments. The encoded protein, TFE, appears to be the canine counterpart of a recently cloned human transcription factor, ITF-2, that binds to the mu E5 kappa E2 motif found in both immunoglobulin heavy and light chains genes enhancers and belongs to the basic-Helix-Loop-Helix family of transcription factors. When TFE protein was produced in a rabbit reticulocyte lysate, it displayed the same specificity of DNA sequence recognition as the beta-galactosidase fusion protein and immobilization of the translation product on nitrocellulose still appeared to be essential for detecting in vitro DNA binding activity. Functional data failed to assign a role for TFE in the control of thyroglobulin gene transcription in vitro, suggesting that the selection of TFE clone resulted from the fortuitous presence of a high affinity binding site in the probe used for screening the expression library. Images

Javaux, F; Donda, A; Vassart, G; Christophe, D

1991-01-01

73

Leptin signaling regulates hypothalamic expression of nescient helix-loop-helix 2 (Nhlh2) through signal transducer and activator 3 (Stat3).  

PubMed

Mice with a deletion of the hypothalamic basic helix-loop-helix transcription factor Nhlh2 display adult onset obesity. We have previously shown that Nhlh2 expression is induced by leptin. In this study, we identify a small proximal leptin-responsive promoter region in the Nhlh2 gene. This 163bp promoter contains five putative binding sites for the leptin-activated Stat3 transcription factor, and two putative binding sites for the NF?B transcription factor. Results of mutagenesis studies reveal that deletion of the NF?B sites have little effect, mutagenesis of the third Stat3 site eliminates both leptin-induced and basal expression of Nhlh2. Mutagenesis of the 4th and 5th sites eliminates leptin-induced expression, and increases basal expression above the WT promoter. Stat3 can be preferentially pulled down from leptin-treated mouse hypothalamic chromatin extracts. This study identifies leptin-induced Stat3 transcription factor as the major transcriptional regulator of Nhlh2. As Nhlh2 transcriptionally regulates genes within the melanocortin pathway, these findings have implications for human body weight control. PMID:24486192

Al Rayyan, Numan; Zhang, Jinhua; Burnside, Amy S; Good, Deborah J

2014-03-25

74

Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts.  

PubMed

Three complete cDNA clones encoding Id-related helix-loop-helix (HLH) proteins lacking a basic region were isolated from a pcD2 cDNA expression library prepared from TIG-3 human diploid fibroblasts (HDF). Of these cDNAs (Id-1H, Id-1H', and Id-2H), two (Id-1H and Id-1H') appeared to be derived by alternative RNA splicing. Id-1H and Id-2H seem to be human homologues of mouse Id-1 and Id-2, respectively, and have potential to encode 154 and 135 amino acid proteins. The Id-1H and Id-2H mRNAs were barely detectable in quiescent early passage HDF; serum coordinately induced both mRNAs, with two peaks of expression, in early and late in G1. Antisense oligomers complementary to Id-1H and Id-2H mRNA prevented early passage HDF from entering the S phase of the cell cycle. The treatment of serum-stimulated early passage cells with the antisense Id-1H oligomer completely abolished Id-1H. In senescent cells, serum barely induced the Id-1H and Id-2H mRNAs, although the levels of c-myc expression induced were similar in early passage and senescent cells. The expression levels of these Id genes vary among immortal human cell lines. Both genes were overexpressed in VA4 SV40-transformed lung fibroblasts and EJ-1 bladder carcinoma cells, while these genes were expressed at a very low level in SVts8 cells derived from SV40 tsA-transformed TIG-3 cells. SVts8 cells may acquire some function redundant to Id proteins. HT1080 fibrosarcoma cells expressed the Id-1H gene but not the Id-2H gene, suggesting these Id genes may subserve redundant functions. PMID:8294468

Hara, E; Yamaguchi, T; Nojima, H; Ide, T; Campisi, J; Okayama, H; Oda, K

1994-01-21

75

Intricate gene regulatory networks of helix-loop-helix (HLH) proteins support regulation of bone-tissue related genes during osteoblast differentiation  

Microsoft Academic Search

Helix-loop-helix (HLH) transcription factors are key regulators of neurogenesis, myogenesis and osteogenesis. Here the relative contributions of multiple classes of HLH factors to the expression of bone related genes during osteoblast maturation were compared. We examined the expression of a panel of HLH proteins (e.g., Twist1\\/2, USF1\\/2, c-Myc, Id1 approximately 4, E12\\/47, Stra13) and one Zn finger protein (Snail which

Ying Zhang; Mohammad Q. Hassan; Zhao-Yong Li; Janet L. Stein; Jane B. Lian; Andre J. Van Wijnen; Gary S. Stein

2008-01-01

76

Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene.  

PubMed Central

The E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements. It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types. We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts. A 73 kDa protein was identified by this analysis: this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells. The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box-binding activity LEF1/BCF1 in these cells; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products. Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis. Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins; the selective appearance of this putative cell-specific transcription factor in B lymphoid cells seems to be attributable, at least in part, to the elevated E2A protein concentrations in these cells. Images

Aronheim, A; Shiran, R; Rosen, A; Walker, M D

1993-01-01

77

Helix-Loop-Helix Factor Inhibitor of Differentiation 3 Regulates Interleukin-5 Expression and B-1a B Cell Proliferation  

PubMed Central

Objective Natural immunity is emerging as an important mediator of protection from atherogenesis. Natural IgM antibodies that recognize oxidation-specific epitopes on low-density lipoprotein or phospholipids and the B-1a B cells that produce them attenuate atherosclerosis. We previously demonstrated that Apoe?/? mice globally deficient in the helix-loop-helix protein inhibitor of differentiation 3 (Id3) develop early diet-induced atherosclerosis. Furthermore, B cell–mediated attenuation of atherosclerosis in B cell–deficient mice was dependent on Id3. Here, we sought to determine whether Id3 regulates B-1a B cells and the natural antibodies that they produce and identify mechanisms mediating these effects. Approach and Results Mice lacking Id3 had significantly fewer B-1a B cells in the spleen and peritoneal cavity and reduced serum levels of the natural antibody E06. B cell–specific deletion of Id3 revealed that this effect was not because of the loss of Id3 in B cells. Interleukin (IL)-33 induced abundant, Id3-dependent IL-5 production in the recently identified innate lymphoid cell, the natural helper (NH) cell, but not Th2 or mast cells. In addition, delivery of IL-5 to Id3-deficient mice restored B-1a B cell proliferation. B-1a B cells were present in aortic samples also containing NH cells. Aortic NH cells produced IL-5, a B-1a B cell mitogen in response to IL-33 stimulation. Conclusions These studies are the first to identify NH and B-1a B cells in the aorta and provide evidence that Id3 is a key regulator of NH cell IL-5 production and B-1a B cell homeostasis.

Perry, Heather M.; Oldham, Stephanie N.; Fahl, Shawn P.; Que, Xuchu; Gonen, Ayelet; Harmon, Daniel B.; Tsimikas, Sotirios; Witztum, Joseph L.; Bender, Timothy P.; McNamara, Coleen A.

2014-01-01

78

Anthocyanin1 of petunia encodes a basic helix-loop-helix protein that directly activates transcription of structural anthocyanin genes  

Microsoft Academic Search

The petunia loci anthocyanin1 ( an1 ), an2 , an4 , and an11 are required for the transcription of anthocyanin biosynthetic genes in floral organs. The an2 and an11 loci were recently cloned and shown to encode a MYB-domain transcriptional activator and a cytosolic WD40 protein, respectively. Here, we report the isolation of an1 by transposon tagging. an1 encodes a

Cornelis Spelt; Francesca Quattrocchio; Joseph N. M. Mol; Ronald Koes

2000-01-01

79

The basic helix-loop-helix-zipper transcription factor USF1 regulates expression of the surfactant protein-A gene.  

PubMed

Expression of the rabbit pulmonary surfactant protein A (SP-A) gene is lung-specific, occurs primarily in type II cells, and is developmentally regulated. We previously identified two E-box-like enhancers, termed the distal binding element (DBE) and proximal binding element (PBE), in the 5'-flanking region of the rabbit SP-A gene. In the present study, the PBE was used to screen a rabbit fetal lung cDNA expression library; a cDNA insert was isolated which is highly similar in sequence to human upstream stimulatory factor 1 (hUSF1). By use of reverse transcription polymerase chain reaction, two isoforms of rabbit USF1 (rUSF1) mRNAs were identified in fetal rabbit lung and other tissues. The levels of rUSF1 mRNAs reach a peak in fetal rabbit lung at 23 days gestation, in concert with the time of initiation of SP-A gene transcription. Binding complexes of nuclear proteins obtained from fetal rabbit lung tissue and isolated type II cells with the DBE and PBE were supershifted by the addition of anti-rUSF1 IgG. Binding activity was enriched in type II cells compared with lung fibroblasts. Overexpression of rUSF1s in A549 adenocarcinoma cells positively regulated SP-A promoter activity of cotransfected reporter gene constructs. It is suggested that rUSF1s, which bind to two E-box elements in the SP-A gene 5'-flanking region, may serve a key role in the regulation of SP-A gene expression in pulmonary type II cells. PMID:9287355

Gao, E; Wang, Y; Alcorn, J L; Mendelson, C R

1997-09-12

80

Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes  

SciTech Connect

The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes. Retinoids, vitamin A analogues, are powerful regulators of cell growth and differentiation and are widely used in the prevention and treatment of a variety of cancers in humans. Furthermore, retinoic acid is necessary for the maintenance of epithelial differentiation and demonstrates an inhibitory action on skin carcinogenesis. We examined the effect of all-trans retinoic acid on expression of ID-1, -2, -3, and -4 in normal human keratinocytes and found that exposure of these cells to all-trans retinoic acid causes an increase in both ID-1 and ID-3 gene expression. Furthermore, our data show that this increase is mediated by increased transcription involving several cis-acting elements in the distal portion of the promoter, including a CREB-binding site, an Egr1 element, and an YY1 site. These data demonstrate that the ID proteins are direct targets of the retinoic acid signaling pathway. Given the importance of the ID proteins to epidermal differentiation, these results suggest that IDs may be mediating some of the effects of all-trans retinoic acid in normal human keratinocytes.

Villano, C.M. [Department of Biochemistry and Microbiology, 76 Lipman Drive, Rutgers, State University of NJ, New Brunswick, NJ 08901 (United States); White, L.A. [Department of Biochemistry and Microbiology, 76 Lipman Drive, Rutgers, State University of NJ, New Brunswick, NJ 08901 (United States)]. E-mail: lawhite@aesop.rutgers.edu

2006-08-01

81

Evidence supporting the existence of a NUPR1-like family of helix-loop-helix chromatin proteins related to, yet distinct from, AT hook-containing HMG proteins.  

PubMed

NUPR1, a small chromatin protein, plays a critical role in cancer development, progression, and resistance to therapy. Here, using a combination of structural bioinformatics and molecular modeling methods, we report several novel findings that enhance our understanding of the biochemical function of this protein. We find that NUPR1 has been conserved throughout evolution, and over time it has undergone duplications and transpositions to form other transcriptional regulators. Using threading, homology-based molecular modeling, molecular mechanics calculations, and molecular dynamics simulations, we generated structural models for four of these proteins: NUPR1a, NUPR1b, NUPR2, and the NUPR-like domain of GTF2-I. Comparative analyses of these models combined with extensive linear motif identification reveal that these four proteins, though similar in their propensities for folding, differ in size, surface changes, and sites amenable for posttranslational modification. Lastly, taking NUPR1a as the paradigm for this family, we built models of a NUPR-DNA complex. Additional structural comparisons revealed that NUPR1 defines a new family of small-groove-binding proteins that share structural features with, yet are distinct from, helix-loop-helix AT-hook-containing HMG proteins. These models and inferences should lead to a better understanding of the function of this group of chromatin proteins, which play a critical role in the development of human malignant diseases. PMID:25056123

Urrutia, Raul; Velez, Gabriel; Lin, Marisa; Lomberk, Gwen; Neira, Jose Luis; Iovanna, Juan

2014-08-01

82

A new transcriptional-activation motif restricted to a class of helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells.  

PubMed Central

Previous studies demonstrated that the amino-terminal portions of E2A and E2-2 are crucial for transactivation. Subsequent findings showed that the same amino-terminal region of E2A is involved in two different translocation events contributing to the induction of a pre-B-cell acute lymphoblastic leukemia and a pro-B-cell acute lymphoblastic leukemia. These results led us to focus on the amino-terminal region of E2A to better understand its normal role in transcriptional regulation and its aberrant involvement in the two leukemias. We report here the identification of two conserved boxes in the E2A amino-terminal domain that show extensive homology within the transactivation domains of E12, E47, E2-2, HEB, and daughterless, all members of the same class of helix-loop-helix proteins. Together, both boxes are crucial for transcriptional activation and have the potential to form a new activation motif, that of a loop adjacent to an amphipathic alpha-helix, designated the loop-helix (LH) motif. A minimal region containing the LH motif is sufficient for transcriptional activation. Point mutations in the amphipathic helix of the minimal region reduce its transactivation capabilities dramatically. The same constructs expressed in yeast cells show identical patterns of activation, suggesting that the LH motif and its target proteins are functionally conserved in yeast cells. We propose that the LH motif represents a novel transactivation domain that is distinct from the previously characterized acidic blob, proline-rich, and glutamine-rich activation motifs. In addition, the LH motif is the first activation motif restricted to one class of DNA binding proteins. Images

Quong, M W; Massari, M E; Zwart, R; Murre, C

1993-01-01

83

A cell-penetrating peptide suppresses the hypoxia inducible factor-1 function by binding to the helix-loop-helix domain of the aryl hydrocarbon receptor nuclear translocator  

PubMed Central

The heterodimeric hypoxia inducible factor-1 (HIF-1) complex is composed of the hypoxia inducible factor-1 alpha (HIF-1?) and the aryl hydrocarbon receptor nuclear translocator (ARNT). Activation of the HIF-1 function is essential for tumor growth and metastasis. We previously showed that transfection of a plasmid containing an ARNT-interacting peptide (Ainp1) cDNA suppresses the HIF-1 signaling in Hep3B cells. Here we generated TAT fusion of the Ainp1 peptide (6His-TAT-Ainp1) to determine whether and how the Ainp1 peptide suppresses the HIF-1 function. The bacterially expressed 6His-TAT-Ainp1 was purified under denatured condition and then refolded by limited dialysis. The refolded 6His-TAT-Ainp1 interacts with the helix-loop-helix (HLH) domain of ARNT in a similar fashion as the native 6His-Ainp1. 6His-TAT-Ainp1 colocalizes with ARNT in the nucleus of HeLa and Hep3B cells after protein transduction. The transduced protein reaches the maximum intracellular levels within 2 h while remains detectable up to 96 h in HeLa cells. At 2 µM concentration, 6His-TAT-Ainp1 is not cytotoxic in HeLa cells but suppresses the cobalt chloride-activated, hypoxia responsive enhancer-driven luciferase expression in a dose-dependent manner. In addition, it decreases the cobalt chloride-dependent induction of the HIF-1 target genes at both the message (vascular endothelial growth factor and aldolase C) and protein (carbonic anhydrase IX and glucose transporter 1) levels. The protein levels of HIF-1? and ARNT are not altered in the presence of 6His-TAT-Ainp1. In summary, we provided evidence to support that the Ainp1 peptide directly suppresses the HIF-1 function by interacting with the ARNT HLH domain, and in turn interfering with the heterodimerization of HIF-1? and ARNT.

Wang, Yu; Thompson, John D.; Chan, William K.

2013-01-01

84

(-)-Epigallocatechin-3-gallate induces Du145 prostate cancer cell death via downregulation of inhibitor of DNA binding 2, a dominant negative helix-loop-helix protein  

PubMed Central

(?)-Epigallocatechin-3-gallate (EGCG) is one of the major polyphenol components in green tea. It effectively induces apoptosis in prostate cancer cells. The anticancer effect of this reagent is appealing because it is a natural component of a popular daily beverage that has proven harmless for thousands of years, making it a good candidate chemopreventive agent. EGCG suppresses cell growth and causes cell death, but the mechanisms are not well characterized, especially in androgen-independent prostate cancer cells. In the present study, using Affymetrix genechip Hu133 2.0, we analyzed the gene expression patterns of the androgen-independent prostate cancer cell line Du145, treated with or without EGCG, and found 40 genes whose expression levels were altered (>twofold, either upregulated or downregulated, P < 0.01) upon treatment with EGCG. These gene products are involved in the functions of transcription, RNA processing, protein folding, phosphorylation, protein degradation, cell motility, and ion transport. Among them, inhibitor of DNA binding 2 (ID2), known as a dominant anti-retinoblastoma (Rb) helix-loop-helix protein, was found to be downregulated fourfold by EGCG treatment. Forced expression of ID2 in Du145 cells reduced apoptosis and increased cell survival in the presence of EGCG, and knockdown ID2 expression in Du145 cells using a morpholino oligonucleotide specific for ID2 mimicked the apoptosis effect generated by EGCG treatment, although it was milder. To our knowledge, this is the first report indicating that ID2 is one of the critical factors in the signaling pathway of Du145 cell death induced by EGCG.

Luo, Katherine L.; Luo, Jian-Hua; Yu, Yan P.

2014-01-01

85

(-)-Epigallocatechin-3-gallate induces Du145 prostate cancer cell death via downregulation of inhibitor of DNA binding 2, a dominant negative helix-loop-helix protein.  

PubMed

(-)-Epigallocatechin-3-gallate (EGCG) is one of the major polyphenol components in green tea. It effectively induces apoptosis in prostate cancer cells. The anticancer effect of this reagent is appealing because it is a natural component of a popular daily beverage that has proven harmless for thousands of years, making it a good candidate chemopreventive agent. EGCG suppresses cell growth and causes cell death, but the mechanisms are not well characterized, especially in androgen-independent prostate cancer cells. In the present study, using Affymetrix genechip Hu133 2.0, we analyzed the gene expression patterns of the androgen-independent prostate cancer cell line Du145, treated with or without EGCG, and found 40 genes whose expression levels were altered (>twofold, either upregulated or downregulated, P < 0.01) upon treatment with EGCG. These gene products are involved in the functions of transcription, RNA processing, protein folding, phosphorylation, protein degradation, cell motility, and ion transport. Among them, inhibitor of DNA binding 2 (ID2), known as a dominant anti-retinoblastoma (Rb) helix-loop-helix protein, was found to be downregulated fourfold by EGCG treatment. Forced expression of ID2 in Du145 cells reduced apoptosis and increased cell survival in the presence of EGCG, and knockdown ID2 expression in Du145 cells using a morpholino oligonucleotide specific for ID2 mimicked the apoptosis effect generated by EGCG treatment, although it was milder. To our knowledge, this is the first report indicating that ID2 is one of the critical factors in the signaling pathway of Du145 cell death induced by EGCG. PMID:20002680

Luo, Katherine L; Luo, Jian-Hua; Yu, Yan P

2010-03-01

86

The TT8 Gene Encodes a Basic Helix-Loop-Helix Domain Protein Required for Expression of DFR and BAN Genes in Arabidopsis Siliques  

Microsoft Academic Search

The TRANSPARENT TESTA8 ( TT8 ) locus is involved in the regulation of flavonoid biosynthesis in Arabidopsis. The tt8-3 allele was isolated from a T-DNA-mutagenized Arabidopsis collection and found to be tagged by an integrative mole- cule, thus permitting the cloning and sequencing of the TT8 gene. TT8 identity was confirmed by complementation of tt8-3 and sequence analysis of an

Nathalie Nesi; Isabelle Debeaujon; Clarisse Jond; Georges Pelletier; Michel Caboche; Loïc Lepiniec

2000-01-01

87

Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product  

NASA Astrophysics Data System (ADS)

THE proteins encoded by the myc gene family are involved in the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms1. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/helix-loop-helix and a leucine zipper motif, respectively. These motifs are involved both in DNA binding and in protein dimerization2-5. In addition, myc protein family members share several regions of highly conserved amino acids in their amino termini that are essential for transformation6,7. We report here that an N-terminal domain present in both the c-myc and N-myc proteins mediates binding to the retinoblastoma gene product, pRb. We show that the human papilloma virus E7 protein competes with c-myc for binding to pRb, indicating that these proteins share overlapping binding sites on pRb. Furthermore, a mutant Rb protein from a human tumour cell line that carried a 35-amino-acid deletion in its C terminus failed to bind to c-myc. Our results suggest that c-myc and pRb cooperate through direct binding to control cell proliferation.

Rustgi, Anil K.; Dyson, Nicholas; Bernards, Rene

1991-08-01

88

BRASSINOSTEROID UPREGULATED1, Encoding a Helix-Loop-Helix Protein, Is a Novel Gene Involved in Brassinosteroid Signaling and Controls Bending of the Lamina Joint in Rice1[W][OA  

PubMed Central

Brassinosteroids (BRs) are involved in many developmental processes and regulate many subsets of downstream genes throughout the plant kingdom. However, little is known about the BR signal transduction and response network in monocots. To identify novel BR-related genes in rice (Oryza sativa), we monitored the transcriptomic response of the brassinosteroid deficient1 (brd1) mutant, with a defective BR biosynthetic gene, to brassinolide treatment. Here, we describe a novel BR-induced rice gene BRASSINOSTEROID UPREGULATED1 (BU1), encoding a helix-loop-helix protein. Rice plants overexpressing BU1 (BU1:OX) showed enhanced bending of the lamina joint, increased grain size, and resistance to brassinazole, an inhibitor of BR biosynthesis. In contrast to BU1:OX, RNAi plants designed to repress both BU1 and its homologs displayed erect leaves. In addition, compared to the wild type, the induction of BU1 by exogenous brassinolide did not require de novo protein synthesis and it was weaker in a BR receptor mutant OsbriI (Oryza sativa brassinosteroid insensitive1, d61) and a rice G protein alpha subunit (RGA1) mutant d1. These results indicate that BU1 protein is a positive regulator of BR response: it controls bending of the lamina joint in rice and it is a novel primary response gene that participates in two BR signaling pathways through OsBRI1 and RGA1. Furthermore, expression analyses showed that BU1 is expressed in several organs including lamina joint, phloem, and epithelial cells in embryos. These results indicate that BU1 may participate in some other unknown processes modulated by BR in rice.

Tanaka, Atsunori; Nakagawa, Hitoshi; Tomita, Chikako; Shimatani, Zenpei; Ohtake, Miki; Nomura, Takahito; Jiang, Chang-Jie; Dubouzet, Joseph G.; Kikuchi, Shoshi; Sekimoto, Hitoshi; Yokota, Takao; Asami, Tadao; Kamakura, Takashi; Mori, Masaki

2009-01-01

89

Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors  

Microsoft Academic Search

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a key enzyme involved in defence against reactive forms of oxygen and inhibition of neoplasia. Under conditions of oxidative stress, expression of NQO1 is induced, and the resulting increase in oxidoreductase protein provides the cell with multiple layers of protection against environmental insults. Firstly, the catalytic activity of NQO1 is directed towards the complete reduction

Paul Nioi; John D. Hayes

2004-01-01

90

Specificity for the Hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression  

SciTech Connect

This report investigates transcriptional repressors in Drosophila melanogaster and their function in and effect on developmental processes such as sex determination. Details on the mechanism of function of these transcriptional repressors are also discussed. 50 refs., 3 figs., 4 tabs.

Dawson, S.R.; Turner, D.L.; Weintraub, H.; Parkhurst, S.M. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)

1995-12-01

91

Responses of a Triple Mutant Defective in Three Iron Deficiency-Induced BASIC HELIX-LOOP-HELIX Genes of the Subgroup Ib(2) to Iron Deficiency and Salicylic Acid  

PubMed Central

Plants are sessile organisms that adapt to external stress by inducing molecular and physiological responses that serve to better cope with the adverse growth condition. Upon low supply of the micronutrient iron, plants actively increase the acquisition of soil iron into the root and its mobilization from internal stores. The subgroup Ib(2) BHLH genes function as regulators in this response, however their concrete functions are not fully understood. Here, we analyzed a triple loss of function mutant of BHLH39, BHLH100 and BHLH101 (3xbhlh mutant). We found that this mutant did not have any iron uptake phenotype if iron was provided. However, under iron deficiency the mutant displayed a more severe leaf chlorosis than the wild type. Microarray-based transcriptome analysis revealed that this mutant phenotype resulted in the mis-regulation of 198 genes, out of which only 15% were associated with iron deficiency regulation itself. A detailed analysis revealed potential targets of the bHLH transcription factors as well as genes reflecting an exaggerated iron deficiency response phenotype. Since the BHLH genes of this subgroup have been brought into the context of the plant hormone salicylic acid, we investigated whether the 3xbhlh mutant might have been affected by this plant signaling molecule. Although a very high number of genes responded to SA, also in a differential manner between mutant and wild type, we did not find any indication for an association of the BHLH gene functions in SA responses upon iron deficiency. In summary, our study indicates that the bHLH subgroup Ib(2) transcription factors do not only act in iron acquisition into roots but in other aspects of the adaptation to iron deficiency in roots and leaves.

Maurer, Felix; Naranjo Arcos, Maria Augusta; Bauer, Petra

2014-01-01

92

Rbms3, an RNA-binding protein, mediates the expression of Ptf1a by binding to its 3'UTR during mouse pancreas development.  

PubMed

The development of the pancreas is a complicated process that is regulated on several levels. Pancreas transcription factor 1, alpha subunit (Ptf1a), also known as p48, is a pancreas-specific basic helix-loop-helix transcription factor that is critical for both exocrine pancreas development and maintenance of acinar cell differentiation. Based on a differential screening assay, we identified Rbms3, a gene encoding a glycine-rich RNA-binding protein, to be specifically expressed in the neural tube and the pancreatic rudiment of e10.5 embryos. The presence of Rbms3 in the early developing pancreas suggests that specific post-transcriptional regulation mechanisms play an important role in controlling pancreas development. In this study, we show that Rbms3 binds to the 3'UTR of Ptf1a mRNA, but not the 3'UTR of Pdx1, which is another pancreatic transcription factor. The ectopic expression of Rbms3 stimulates the translation of a reporter gene carrying the Ptf1a 3'UTR. In addition, when Rbms3 expression is suppressed in the AR42J-B13 pancreatic exocrine cell line, the expression of Ptf1a is also down-regulated. These results suggest that binding of Rbms3 to the 3'UTR of Ptf1a regulates the production of the Ptf1a protein and, thereby, indirectly regulates the expression of the Ptf1a downstream target genes. PMID:22372950

Lu, Chung-Kuang; Lai, Yi-Chyi; Chen, Hau-Ren; Chiang, Ming-Ko

2012-07-01

93

Antagonistic Regulation of ?-Globin Gene Expression by Helix-Loop-Helix Proteins USF and TFII-I  

PubMed Central

The human ?-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the ?-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased ?-globin gene expression, while diminishing TFII-I activity increased ?-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult ?-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the ?-globin gene locus and play important roles in restricting ?-globin gene expression to the adult stage of erythropoiesis.

Crusselle-Davis, Valerie J.; Vieira, Karen F.; Zhou, Zhuo; Anantharaman, Archana; Bungert, Jorg

2006-01-01

94

Oligomerization Mediated by a Helix-Loop-Helix-Like Domain of Baculovirus IE1 Is Required for Early Promoter Transactivation  

Microsoft Academic Search

IE1 is a principal transcriptional regulator of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Transactivation by IE1 is stimulated when early viral promoters are cis linked to homologous- region (hr) enhancer sequences of AcMNPV. This transcriptional enhancement is correlated with the binding of IE1 as a dimer to the 28-bp palindromic repeats comprising the hr enhancer. To define the role of homophilic

VICTORIA A. OLSON; JUSTIN A. WETTER; PAUL D. FRIESEN

2001-01-01

95

Production and initial structural characterization of the TM4TM5 helix-loop-helix domain of the translocator protein.  

PubMed

Mainly present in the mitochondria, the translocator protein, TSPO, previously known as the peripheral benzodiazepine receptor, is a small essential membrane protein, involved in the translocation of cholesterol across mitochondrial membranes, a rate determining step in steroids biosynthesis. We previously reported the structure of five fragments encompassing the five putative transmembrane helices and showed that each of these fragments constitutes an autonomous folding unit. To further characterize the structural determinants responsible for helix-helix association of this membrane protein, we now investigate the folding of double transmembrane domains in various detergent micelles. Herein, we present the successful biosynthesis of a double transmembrane domain encompassing the last two C-terminal helices (TM4TM5). For optimal production of this domain in Escherichia coli, the evaluation of various peptide constructs, including TM4TM5 fused to different purification tags or to solubilizing proteins, was necessary. The protocol of production of TM4TM5 with more than 95% purity is reported. This domain was further characterized using circular dichroism and solution state NMR. Far-UV circular dichroism studies indicate that the secondary structure of TM4TM5 is highly helical when solubilized in various detergent micelles including n-dodecyl-?-d-maltoside, n-octyl-?-d-glucoside, n-dodecylphosphocholine, 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), and 1-palmitoyl-2-hydroxy-sn-glycero-3-phospho-(1'-rac-glycerol). In addition, the solubilization conditions of the domain were optimized for NMR experiments, and preliminary analysis indicates that TM4TM5 adopts a stable tertiary fold within the TM4TM5-DHPC complex. PMID:23315717

Galvagnion, C; Montaville, P; Coïc, Y-M; Jamin, N

2013-02-01

96

Receptor Editing and Marginal Zone B Cell Development Are Regulated by the Helix-Loop-Helix Protein, E2A  

Microsoft Academic Search

Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate that E2A ??? B cells that express an autoreactive B cell receptor fail to mature due in part to an inability to activate secondary immunoglobulin (Ig) light chain gene rearrangement. Both RAG1\\/2 gene expression and RS deletion are severely defective in

Melanie W. Quong; Annica Martensson; Anton W. Langerak; Richard R. Rivera; David Nemazee; Cornelis Murre

97

Basic pentacysteine proteins mediate MADS domain complex binding to the DNA for tissue-specific expression of target genes in Arabidopsis.  

PubMed

Basic pentacysteine (BPC) transcription factors have been identified in a large variety of plant species. In Arabidopsis thaliana there are seven BPC genes, which, except for BPC5, are expressed ubiquitously. BPC genes are functionally redundant in a wide range of developmental processes. Recently, we reported that BPC1 binds to guanine and adenine (GA)-rich consensus sequences in the seedstick (STK) promoter in vitro and induces conformational changes. Here we show by chromatin immunoprecipitation experiments that in vivo BPCs also bind to the consensus boxes, and when these were mutated, expression from the STK promoter was derepressed, resulting in ectopic expression in the inflorescence. We also reveal that short vegetative phase (SVP) is a direct regulator of STK. SVP is a floral meristem identity gene belonging to the MADS box gene family. The SVP-APETALA1 (AP1) dimer recruits the SEUSS (SEU)-LEUNIG (LUG) transcriptional cosuppressor to repress floral homeotic gene expression in the floral meristem. Interestingly, we found that GA consensus sequences in the STK promoter to which BPCs bind are essential for recruitment of the corepressor complex to this promoter. Our data suggest that we have identified a new regulatory mechanism controlling plant gene expression that is probably generally used, when considering BPCs' wide expression profile and the frequent presence of consensus binding sites in plant promoters. PMID:23054472

Simonini, Sara; Roig-Villanova, Irma; Gregis, Veronica; Colombo, Bilitis; Colombo, Lucia; Kater, Martin M

2012-10-01

98

Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 å resolution  

Microsoft Academic Search

Background: The sterol regulatory element binding proteins (SREBPs) are helix–loop–helix transcriptional activators that control expression of genes encoding proteins essential for cholesterol biosynthesis\\/uptake and fatty acid biosynthesis. Unlike helix–loop–helix proteins that recognize symmetric E-boxes (5?-CANNTG-3?), the SREBPs have a tyrosine instead of a conserved arginine in their basic regions. This difference allows recognition of an asymmetric sterol regulatory element (StRE

A Parraga; L Bellsolell; AR Ferré-D'Amaré; Stephen K Burley

1998-01-01

99

A heteromeric complex containing the centromere binding factor 1 and two basic leucine zipper factors, Met4 and Met28, mediates the transcription activation of yeast sulfur metabolism.  

PubMed Central

Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing that it acts as a transcription activator, the precise function in transcription of the multi-functional factor Cbf1 remains more elusive. We report here the identification of a new transcription factor Met28 which participates in the regulation of sulfur metabolism. Cloning and sequencing of MET28 revealed that it encodes a new member of the basic leucine zipper DNA binding factor family. We also demonstrate that Met28 possesses no intrinsic transcription activation capabilities. Studies of the DNA binding characteristics of Met28 led us to identify in gel mobility assays a heteromeric complex containing Cbf1, Met4 and Met28. We further demonstrated that the presence of Cbf1 and Met4 stimulates the binding of Met28 to DNA. 'Two-hybrid' studies allowed us to carry out preliminary investigations on the binary protein-protein interactions involved in the formation of the Cbf1-Met4-Met28 complex. Our results give evidence that the leucine zippers of Met4 and Met28, along with the basic helix-loop-helix domain of Cbf1, provide the protein surfaces mediating these interactions. All these results suggest that the multi-functional factor Cbf1 functions in transcription activation by tethering specific activating factors to the DNA. Images

Kuras, L; Cherest, H; Surdin-Kerjan, Y; Thomas, D

1996-01-01

100

Protein- mediated enamel mineralization  

PubMed Central

Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth.

Moradian-Oldak, Janet

2012-01-01

101

Molecular regulation of vasculogenic mimicry in human uveal melanoma cells: role of helix–loop–helix Id2 (inhibitor of DNA binding 2)  

Microsoft Academic Search

Background  Vasculogenic mimicry (VM) is a tumor angiogenesis process in which highly aggressive melanoma cells form patterned, tubular\\u000a networks in an in vitro, three-dimensional culture that mimics vasculogenic networks formed by endothelial cells. These cells\\u000a also express endothelial cell-associated genes such as vascular endothelial–cadherin (VE–cadherin) and are correlated with\\u000a poor clinical prognosis in patients. However, the molecular underpinnings of this phenomenon

Fan Su; Bin Li; Jian Wang; Xiaolin Xu; Ruojin Ren; Liaoqing Li; Fei Gao; Xiaochao Liu

2009-01-01

102

Expression of Helix-Loop-Helix Factor Id-i Is Dependent on the Hepatocyte Proliferation and Differentiation Status in Rat Liver and in Primary Culture1  

Microsoft Academic Search

Id proteins are known as negative regulators of differentiation in various cell types. In this report, we show that the Id-i gene was down regulated during the development of rat liver. No Id-i transcripts were detected in terminal differentiated hepatocytes. We have studied Id-i expression in proliferating hepatocytes using an in vivo model of liver regeneration after partial hepatectomy and

Catherine Le Jossic; Gennady P. Ilyin; Pascal Loyer; Denise Glaise; Sandrine Cariou; Christiane Guguen-Guillouzo

103

Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS\\/ets protein in Ewing sarcoma  

Microsoft Academic Search

The chromosomal translocation specifically linked to the Ewing sarcoma family results in the generation of fusion proteins comprising the amino terminal portion of EWS and the DNA-binding domain of ets transcription factors. The EWS\\/ets chimeric proteins act as aberrant transcription factors leading to tumorigenic processes. We searched for genes specifically activated in Ewing sarcoma cells but not in other tumor

Mariko Fukuma; Hajime Okita; Jun-ichi Hata; Akihiro Umezawa

2003-01-01

104

NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively  

SciTech Connect

NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.

Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)] [and others] [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); and others

1997-03-01

105

Sense organ identity in the Drosophila antenna is specified by the expression of the proneural gene atonal  

Microsoft Academic Search

We have shown that the basic helix–loop–helix transcription factor Atonal is sufficient for specification of one of the three subsets of olfactory sense organs on the Drosophila antenna. Misexpression of Atonal in all sensory precursors in the antennal disc results in their conversion to coeloconic sensilla. The mechanism by which specific sense organ fate is triggered remains unclear. We have

Dhanisha Jhaveri; Anindya Sen; G. Venugopala Reddy; Veronica Rodrigues

2000-01-01

106

olig2 Is Required for Zebrafish Primary Motor Neuron and Oligodendrocyte Development  

Microsoft Academic Search

Oligodendrocytes are produced from the same region of the ventral spinal cord that earlier generated motor neurons in bird and rodent embryos. Motor neuron and oligodendrocyte precursor cells express Olig genes, which encode basic helix–loop–helix transcription factors that play important roles in the development of both motor neurons and oligodendrocytes. We found that oligodendrocytes develop similarly in zebrafish embryos, in

Hae-Chul Park; Amit Mehta; Joanna S. Richardson; Bruce Appel

2002-01-01

107

Role of Id Proteins in Breast Cancer.  

National Technical Information Service (NTIS)

E2A gene products (E47 and E12) are potent transcription factors containing the basic helix-loop-helix (bHLH) domain for DNA binding and dimerization. E2A proteins are thought to control cell growth and differentiation. E2A is also implicated to have a ro...

X. H. Sun

2000-01-01

108

Role of ID Proteins in Breast Cancer.  

National Technical Information Service (NTIS)

The basic helix-loop-helix transcription factors, E12 and E47 (products of the E2A gene), have been implicated to have a role as tumor suppressors. Conversely, the inhibitors of El2 and E47, the Id proteins, have been shown to stimulate cell growth, and c...

X. Sun

1999-01-01

109

Role of Id Proteins in Breast Cancer.  

National Technical Information Service (NTIS)

E2A gene products (E47 and E12) are potent transcription factors containing the basic helix-loop-helix (bHLH) domain for DNA binding and dimerization. E2A proteins are thought to control cell growth and differentiation. E2A is also implicated to have a ro...

S. Xiao-Hong

2001-01-01

110

Protein-mediated boundary lubrication in arthroplasty.  

PubMed

Wear of articulated surfaces can be a major lifetime-limiting factor in arthroplasty. In the natural joint, lubrication is effected by the body's natural synovial fluid. Following arthroplasty, and the subsequent reformation of the synovial membrane, a fluid of similar composition surrounds the artificial joint. Synovial fluid contains, among many other constituents, a substantial concentration of the readily adsorbing protein albumin. The ability of human serum albumin to act as a boundary lubricant in joint prostheses has been investigated using a pin-on-disc tribometer. Circular dichroism spectroscopy was employed to follow the temperature- and time-dependent conformational changes of human serum albumin in the model lubricant solution. Effects of protein conformation and polymer surface hydrophilicity on protein adsorption and the resulting friction in the boundary lubrication regime have been investigated. Unfolded proteins preferentially adsorb onto hydrophobic polymer surfaces, where they form a compact, passivating layer and increase sliding friction-an effect that can be largely suppressed by rendering the substrate more hydrophilic. A molecular model for protein-mediated boundary friction is proposed to consolidate the observations. The relevance of the results for in vivo performance and ex vivo hip-joint testing are discussed. PMID:15451636

Heuberger, M P; Widmer, M R; Zobeley, E; Glockshuber, R; Spencer, N D

2005-04-01

111

Mechanics of Protein-Mediated DNA Looping  

NASA Astrophysics Data System (ADS)

The formation of looped DNA-protein complexes in which a protein or protein assembly binds to multiple distant operator sites on the DNA is a common feature for many regulatory schemes on the transcriptional level. In a living cell, a multitude of mechanical forces and constraints act on these complexes, and it is imperative to understand their effects on biological function. For this aim, we study the lactose repressor as a model system for protein-mediated DNA looping in single-molecule experiments. Using a novel axial constant-force optical trapping scheme that allows us to manipulate sub-micron DNA fragments with well-controlled forces down to the 10 fN range, we show that mechanical tension in the substrate DNA of hundred femtonewton is sufficient to disrupt the loop formation process, which suggests that such mechanical tension may provide a mechanical pathway to controlling gene expression in vivo. From the force sensitivity of the loop formation process, we can also infer the topology of the looped complex; in our case an antiparallel conformation. In addition, we will present new tethered-particle microscopy data that shows lifetimes of the looped complexes that are two to three orders of magnitude shorter than those measured in biochemical competition assays and discuss possible interpretations, including the suggestion that operator binding of the lactose repressor tetramer leads to a destabilization of the dimer-dimer interface and that thus the loop breakdown process is mostly a dissociation of the tetramer into two dimers, instead, as widely assumed, an unbinding of the tetramer from the DNA.

Meiners, Jens-Christian

2009-03-01

112

Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold.  

PubMed

Three oxidative products of 5-methylcytosine (5mC) occur in mammalian genomes. We evaluated if these cytosine modifications in a CG dinucleotide altered DNA binding of four B-HLH homodimers and three heterodimers to the E-Box motif CGCAG|GTG. We examined 25 DNA probes containing all combinations of cytosine in a CG dinucleotide and none changed binding except for carboxylation of cytosine (5caC) in the strand CGCAG|GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3|Ascl1 heterodimer which increased binding ~10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors. PMID:24835951

Golla, Jaya Prakash; Zhao, Jianfei; Mann, Ishminder K; Sayeed, Syed K; Mandal, Ajeet; Rose, Robert B; Vinson, Charles

2014-06-27

113

1H NMR spectroscopic studies of calcium-binding proteins. 1. Stepwise proteolysis of the C-terminal alpha-helix of a helix-loop-helix metal-binding domain.  

PubMed

A series of modified parvalbumins, differing only in length of alpha-helix F at the C-terminus, was prepared by carboxypeptidase-mediated digestions of the beta-lineage parvalbumin (pI = 4.25) from carp (N; 108 residues). Removal of Ala-108 to form the N-1 derivative (des-Ala108,Lys107-parvalbumin) only slightly alters the protein's ability to chelate Ca(II) or lanthanides(III). Analysis of the kinetics of their Yb(III) off-rates by optical stopped-flow techniques, determination of their Lu(III)-binding constants by high-resolution 1H NMR methods, and inspection of their solution structures by Yb(III)-shifted 1H NMR techniques indicate N-1 and N-2 are very similar to N (0.1-0.2 M KCl; pH 6-7; 23-55 degrees C). However, removal of the next one or two residues, Val-106 or Val-106/Leu-105, to generate the N-3 and N-4 derivatives severely alters the metal ion binding characteristics of the protein. Although two Yb(III) off-rates are observed for N-3, both are faster than that for the unmodified protein: kCD by a factor of 2 and kEF by a factor of 2200. Removal of Ala-104 and Ala-104/Thr-103 to give a mixture of N-5 and N-6 derivatives eliminates the slow-release site altogether, the single observable koff being 20-30 times faster than release of Yb(III) from the CD site of native parvalbumin. Removal of the C-terminal alpha-helix by digestion through Phe-102 to give N-7 destabilizes the entire protein structure as judged both by the random-coil appearance of its 1H NMR spectrum and by its aberrant kinetics. Although one abnormally fast koff is still observed at micromolar concentrations, Ln(III) chelation tends to precipitate N-7 at higher parvalbumin concentrations (1-3 mM). In contrast to the critical instability of the N-3 through N-7 derivatives, the remarkable stability of the N-1 and N-2 forms of carp parvalbumin may be attributed to the maintainance of two key structural features: an ion pair bond between the negatively charged C-terminal carboxyl function and the protonated epsilon-NH3+ of Lys-27 and hydrophobic interactions of the inner side of helix F with residues in the protein's core. PMID:3707912

Corson, D C; Williams, T C; Kay, L E; Sykes, B D

1986-04-01

114

A Role for Id Proteins in Mammary Gland Physiology and Tumorigenesis  

Microsoft Academic Search

Id helix-loop-helix (HLH) proteins are regulators of cell growth and differentiation in embryonic and adult tissues. They are members of the basic HLH family of transcription factors but lack a DNA binding domain. By binding to basic HLH transcription factors, Id proteins regulate gene expression. Id1 and Id3 have extensive sequence homology and similar patterns of expression during embryogenesis and

Paola de Candia; Robert Benera; David B. Solit

2004-01-01

115

Id transcriptional regulators in adipogenesis and adipose tissue metabolism.  

PubMed

Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcriptional regulators that lack a basic DNA binding domain. They act as negative regulators of basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibit their DNA binding and transcriptional activity. Id proteins areimplicated in the regulation of various cellular mechanisms such as cell proliferation, cellular differentiation, cell fate determination, angiogenesis and tumorigenesis. A handful of recent studies also disclosed that Id proteins have critical functions in adipocyte differentiation and adipose tissue metabolism. Here, we reviewed the progress made thus far in understanding the specific functions of Id proteins in adipose tissue differentiation and metabolism. In addition to reviewing the known mechanisms of action, we also discuss possible additional mechanisms in which Id proteins might participate in regulating adipogenic and metabolic pathways. PMID:24896358

Patil, Mallikarjun; Sharma, Bal Krishan; Satyanarayana, Ande

2014-01-01

116

Hypoxia-induced activation of HIF-1: role of HIF-1?-Hsp90 interaction  

Microsoft Academic Search

The protein chaperone heat shock protein 90 (Hsp90) is a major regulator of different transcription factors such as MyoD, a basic helix loop helix (bHLH) protein, and the bHLH-Per-aryl hydrocarbon nuclear translocator (ARNT)-Sim (PAS) factors Sim and aryl hydrocarbon receptor (Ahr). The transcription factor hypoxia-inducible factor-1? (HIF-1?), involved in the response to hypoxia, also belongs to the bHLH-PAS family. This

E Minet; D Mottet; G Michel; I Roland; M Raes; J Remacle; C Michiels

1999-01-01

117

Iron assimilation and transcription factor controlled synthesis of riboflavin in plants  

Microsoft Academic Search

Iron homeostasis is vital for many cellular processes and requires a precise regulation. Several iron efficient plants respond\\u000a to iron starvation with the excretion of riboflavin and other flavins. Basic helix–loop–helix transcription factors (TF) are\\u000a involved in the regulation of many developmental processes, including iron assimilation. Here we describe the isolation and\\u000a characterisation of two Arabidopsis bHLH TF genes, which

A. Vorwieger; C. Gryczka; A. Czihal; D. Douchkov; J. Tiedemann; H.-P. Mock; M. Jakoby; B. Weisshaar; I. Saalbach; H. Bäumlein

2007-01-01

118

Isolation and characterization of IRO2, a novel iron-regulated bHLH transcription factor in graminaceous plants  

Microsoft Academic Search

To clarify the molecular mechanism that regulates iron (Fe) acquisition in graminaceous plants, a time-course analysis of gene expression during Fe deficiency stress was conducted using a rice 22K oligo-DNA microarray. Twenty-one genes for proteins that func- tion in gene regulation were induced by Fe deficiency. Of these genes, a putative basic helix-loop-helix (bHLH) transcription factor gene, named OsIRO2, was

Yuko Ogo; Reiko Nakanishi Itai; Hiromi Nakanishi; Haruhiko Inoue; Takanori Kobayashi; Motofumi Suzuki; Michiko Takahashi; Satoshi Mori; Naoko K. Nishizawa

2006-01-01

119

Overexpression of N-Myc Rapidly Causes Acute Myeloid Leukemia in Mice  

Microsoft Academic Search

N-MYC encodes a basic helix-loop-helix\\/leucine zipper (bHLH\\/ LZ) transcription factor that is frequently overexpressed in human neuroblastoma. N-MYC overexpression has also been reported in human acute myeloid leukemias (AML), which we show here is a frequent event. Myeloid cells in N-Myc- overexpressing mouse bone marrow hyperproliferate but those in c-MYC-overexpressing bone marrow do not. The NH2-terminal transactivation domain, nuclear localization

Hiroyuki Kawagoe; Ayten Kandilci; Tanya A. Kranenburg; Gerard C. Grosveld

2007-01-01

120

Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis  

Microsoft Academic Search

atonal is a Drosophila proneural gene that belongs to the family of basic helix-loop-helix (bHLH)- containing proteins. It is expressed in the chordotonal organs and photoreceptor cells, and flies that lack Atonal protein are ataxic and blind. Here we report the cloning of atonal homologs from red flour beetle, puffer fish, chicken, mouse, and human. The bHLH domain is conserved

Nissim Ben-Arie; Alanna E. McCall; Scott Berkman; Gregor Eichele; Hugo J. Bellen; Huda Y. Zoghbi

1996-01-01

121

Negative Regulation of atonal in Proneural Cluster Formation of Drosophila R8 Photoreceptors  

Microsoft Academic Search

atonal (ato) encodes a basic helix-loop-helix protein and is required for the specification of R8 photoreceptor cells in Drosophila. In the eye imaginal discs, expression of Ato protein is initially in a dorsoventral stripe of cells anterior to the morphogenetic furrow (MF). In the MF, this stripe expression is resolved into regularly spaced clusters of Ato-positive cells, the proneural clusters,

Chien-Kuo Chen; Cheng-Ting Chien

1999-01-01

122

Atonal homolog 1 Is a Tumor Suppressor Gene  

Microsoft Academic Search

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti- oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor

Wouter Bossuyt; Avedis Kazanjian; Natalie De Geest; Sofie Van Kelst; Gert De Hertogh; Karel Geboes; Greg P. Boivin; Judith Luciani; Francois Fuks; Marinee Chuah; Thierry VandenDriessche; Peter Marynen; Jan Cools; Noah F. Shroyer; Bassem A. Hassan

2009-01-01

123

Genetic Mapping of Four Mouse bHLH Genes Related to DrosophilaProneural Gene atonal  

Microsoft Academic Search

It has been shown that mammalian neurogenesis is partly controlled by multiple basic helix–loop–helix (bHLH) genes, as inDrosophila.Recently, mouse homologs ofDrosophila atonal,a proneural gene encoding a bHLH protein required for chordotonal organ and photoreceptor development, have been characterized to obtain further insights into the molecular nature of mammalian neurogenesis. Here, to assess their potential involvement in genetic neural disorders, we

Fumiaki Isaka; Chikara Shimizu; Shigetada Nakanishi; Ryoichiro Kageyama

1996-01-01

124

The oligodendrocyte-specific G protein–coupled receptor GPR17 is a cell-intrinsic timer of myelination  

Microsoft Academic Search

The basic helix-loop-helix transcription factor Olig1 promotes oligodendrocyte maturation and is required for myelin repair. We characterized an Olig1-regulated G protein–coupled receptor, GPR17, whose function is to oppose the action of Olig1. Gpr17 was restricted to oligodendrocyte lineage cells, but was downregulated during the peak period of myelination and in adulthood. Transgenic mice with sustained Gpr17 expression in oligodendrocytes exhibited

Ying Chen; Heng Wu; Shuzong Wang; Hisami Koito; Jianrong Li; Feng Ye; Jenny Hoang; Sabine S Escobar; Alexander Gow; Heather A Arnett; Bruce D Trapp; Nitin J Karandikar; Jenny Hsieh; Q Richard Lu

2009-01-01

125

Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis  

Microsoft Academic Search

Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically,\\u000a there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective,\\u000a targeted, and non-toxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors,\\u000a has recently been shown to be a key regulator of the metastatic

Sean D. McAllister; Ryuichi Murase; Rigel T. Christian; Darryl Lau; Anne J. Zielinski; Juanita Allison; Carolina Almanza; Arash Pakdel; Jasmine Lee; Chandani Limbad; Yong Liu; Robert J. Debs; Dan H. Moore; Pierre-Yves Desprez

2011-01-01

126

The overexpression of AP4 as a prognostic indicator for gastric carcinoma  

Microsoft Academic Search

As a transcription factor belonging to the basic helix-loop-helix leucine-zipper subgroup, AP-4 can control target gene expression\\u000a by altering cell signal transduction, and regulate growth, development, and cell apoptosis. Under pathological circumstances,\\u000a it is involved in tumorigenesis. Herein, immunohistochemistry and real-time PCR were used to detect the transcription factor\\u000a AP-4 expression in gastric cancer, and these data were examined for

Liu Xinghua; Zhang Bo; Guo Yan; Wu Lei; Wu Changyao; Liang Qi; Ye Lin; Tao Kaixiong; Wang Guobin; Chen Jianying

127

Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer  

Microsoft Academic Search

ID4 gene is a member of the inhibitor of DNA-binding (ID) family, which inhibits DNA binding of basic helix–loop–helix transcription factors. Certain human primary breast cancers reportedly have low or no expression of ID4 protein, but its role in carcinogenesis and cancer progression is unknown. To determine its possible role, we examined epigenetic inactivation of ID4 gene by promoter hypermethylation

Naoyuki Umetani; Takuji Mori; Kazuo Koyanagi; Masaru Shinozaki; Joseph Kim; Armando E Giuliano; Dave S B Hoon; DSB Hoon

2005-01-01

128

Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?  

Microsoft Academic Search

The molecular mechanisms that underlie tumour progression are still poorly understood, but recently our knowledge of particular aspects of some of these processes has increased. Specifically, the identification of Snail, ZEB and some basic helix-loop-helix (bHLH) factors as inducers of epithelial–mesenchymal transition (EMT) and potent repressors of E-cadherin expression has opened new avenues of research with potential clinical implications.

Héctor Peinado; David Olmeda; Amparo Cano

2007-01-01

129

Id2 and Id3 Inhibit Development of CD34 1 Stem Cells into Predendritic Cell (Pre-DC)2 but Not into Pre-DC1: Evidence for a Lymphoid Origin of Pre-DC2  

Microsoft Academic Search

We found previously that Id3, which inhibits transcriptional activities of many basic helix- loop-helix transcription factors, blocked T and B cell development but stimulated natural killer (NK) cell development. Here we report that ectopic expression of Id3 and another Id protein, Id2, strongly inhibited the development of primitive CD34 1 CD38 2 progenitor cells into CD123 high dendritic cell (DC)2

Hergen Spits; Franka Couwenberg; Arjen Q. Bakker; Kees Weijer; Christel H. Uittenbogaart

130

Epstein-Barr Virus Latent Membrane Protein 1 Induces Synthesis of Hypoxia-Inducible Factor 1  

Microsoft Academic Search

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1 and HIF-1 that is the central regulator of responses to hypoxia. The specific binding of HIF-1 to the hypoxia-responsive element (HRE) induces the transcription of genes that respond to hypoxic conditions, including vascular endothelial growth factor (VEGF). Here we report that expression of HIF-1 is increased

Naohiro Wakisaka; Satoru Kondo; Tomokazu Yoshizaki; Shigeyuki Murono; Mitsuru Furukawa; Joseph S. Pagano

2004-01-01

131

Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF  

Microsoft Academic Search

Tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1\\/gp75) and dopachrome tautomerase (DCT\\/ TYRP2) belong to a family of melanocyte-specific gene products involved in melanin pigmentation. During melanocyte development expression of tyrosinase family genes is thought to be orches- trated in part by the binding of a shared basic helix-loop-helix transcription factor MITF to the M box, a regulatory element conserved among these genes.

Dong Fang; Yoshiaki Tsuji; Vijayasaradhi Setaluri

2002-01-01

132

Spatial Distribution and Function of Sterol Regulatory Element-Binding Protein 1a and 2 Homo and Heterodimers by In Vivo Two-Photon Imaging and Spectroscopy Fluorescence Resonance Energy Transfer  

Microsoft Academic Search

Sterol regulatory element-binding proteins (SREBPs) are a subfamily of basic helix-loop-helix-leucine zipper proteins that regulate lipid metabolism. We show novel evidence of the in vivo occurrence and sub- nuclear spatial localization of both exogenously expressed SREBP-1a and -2 homodimers and heterodimers obtained by two-photon imaging and spectroscopy fluorescence resonance energy transfer. SREBP-1a ho- modimers localize diffusely in the nucleus, whereas

Aikaterini Zoumi; Shrimati Datta; Lih-Huei L. Liaw; Cristen J. Wu; Gopi Manthripragada; Timothy F. Osborne; Vickie J. LaMorte

2005-01-01

133

Structure of the human gene encoding sterol regulatory element binding protein-1 ( SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13  

Microsoft Academic Search

Sterol regulatory element binding protein-1 (SREBP1) and SREBP2 are structurally related proteins that control cholesterol homeostasis by stimulating transcription of sterol-regulated genes, including those encoding the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl CoA synthase. SREBP1 and SREBP2 are 47% identical, and they share a novel structure comprising a transcriptionally active NH2-terminal basic helix—loop—helix—leucine zipper (bHLH-Zip) domain followed by a membrane

Xianxin Hua; Jian Wu; Joseph L. Goldstein; Michael S. Brown; Helen H. Hobbs

1995-01-01

134

Delayed Onset of Experimental Autoimmune Encephalomyelitis in Olig1 Deficient Mice  

Microsoft Academic Search

BackgroundOlig1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated.Methodology\\/Principal FindingsHere we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in

Xiaoli Guo; Chikako Harada; Kazuhiko Namekata; Yoshinori Mitamura; Hiroshi Yoshida; Yoh Matsumoto; Takayuki Harada

2010-01-01

135

Comparative and Evolutionary Analysis of the HES\\/HEY Gene Family Reveal Exon\\/Intron Loss and Teleost Specific Duplication Events  

Microsoft Academic Search

BackgroundHES\\/HEY genes encode a family of basic helix-loop-helix (bHLH) transcription factors with both bHLH and Orange domain. HES\\/HEY proteins are direct targets of the Notch signaling pathway and play an essential role in developmental decisions, such as the developments of nervous system, somitogenesis, blood vessel and heart. Despite their important functions, the origin and evolution of this HES\\/HEY gene family

Mi Zhou; Jun Yan; Zhaowu Ma; Yang Zhou; Nibras Najm Abbood; Jianfeng Liu; Li Su; Haibo Jia; An-Yuan Guo

2012-01-01

136

Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth  

Microsoft Academic Search

In the developing nervous system, Id2 (inhibitor of DNA binding 2, also known as inhibitor of differentiation 2) enhances cell proliferation, promotes tumour progression and inhibits the activity of neurogenic basic helix-loop-helix (bHLH) transcription factors. The anaphase promoting complex\\/cyclosome and its activator Cdh1 (APC\\/CCdh1) restrains axonal growth but the targets of APC\\/CCdh1 in neurons are unknown. Id2 and other members

Anna Lasorella; Judith Stegmüller; Daniele Guardavaccaro; Guangchao Liu; Maria S. Carro; Gerson Rothschild; Luis de La Torre-Ubieta; Michele Pagano; Azad Bonni; Antonio Iavarone

2006-01-01

137

Bone Marrow–Derived Mesenchymal Stem Cells Transduced With Scleraxis Improve Rotator Cuff Healing in a Rat Model  

Microsoft Academic Search

Background: Rotator cuffs heal through a scar tissue interface after repair that makes them prone to failure. Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is thought to direct tendon development during embryogenesis. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with adenoviral-mediated scleraxis (Ad-Scx) could improve regeneration of the

Lawrence V. Gulotta; David Kovacevic; Jonathan D. Packer; Xiang Hua Deng; Scott A. Rodeo

2011-01-01

138

Mmip-2, a novel RING finger protein that interacts with mad members of the Myc oncoprotein network  

Microsoft Academic Search

Mad proteins are basichelixloophelix – leucine zipper (bHLH-ZIP)-containing members of the myc oncoprotein network. They interact with the bHLH-ZIP protein max, compete for the same DNA binding sites as myc-max heterodimers and down-regulate myc-responsive genes. Using the bHLH-ZIP domain of mad1 as a yeast two-hybrid `bait', we identified Mmip-2, a novel RING finger protein

Xiao-Ying Yin; Kalpana Gupta; Wei Ping Han; Edwin S Levitan; Edward V Prochownik

1999-01-01

139

Cloning and characterization of the mouse ret finger protein (rfp), a B box zinc finger protein  

Microsoft Academic Search

An important question in biology is to understand the role of specific gene products in regulating embryogenesis and cellular differentiation. Many of the regulatory proteins possess specific motifs, such as the homeodomain, basic helix-loop-helix structure, zinc finger, and leucine zipper. These sequence motifs participate in specific protein-DNA, protein-RNA, and protein-protein interactions, and are important for the function of these regulatory

Tongyu Cao

1996-01-01

140

NeuroD1\\/b2 Contributes to Cell-Specific Transcription of the Proopiomelanocortin Gene  

Microsoft Academic Search

NeuroD1\\/b2 is a basic helix-loop-helix (bHLH) factor expressed in the endocrine cells of the pancreas and in a subset of neurons as they undergo terminal differentiation. We now show that NeuroD1 is expressed in corticotroph cells of the pituitary gland and that it is involved in cell-specific transcription of the proopio- melanocortin (POMC) gene. It was previously shown that corticotroph-specific

GINO POULIN; BENJAMIN TURGEON; JACQUES DROUIN

1997-01-01

141

Expression of AMD 1, a gene for a MyoD 1-related factor in the ascidian Halocynthia roretzi  

Microsoft Academic Search

We have isolated and cloned a gene, designated AMD1 (ascidian MyoD-related factor 1), and its cDNAs that encode a member of the family of myogenic basic helix-loop-helix (bHLH) factors from the ascidian Halocynthia roretzi. The AMD1 gene consists of four exons and is transcribed into at least two distinct mRNAs, which differ in their 3' untranslated region. The gene encodes

sato Araki; Hidetoshi Saiga; Kazuhiro W. Makabe; Noriyuki Satoh

1994-01-01

142

A Role for bHLH Transcription Factors in Retinal Degeneration and Dysfunction  

Microsoft Academic Search

The basic helix loop helix (bHLH) transcription factors collectively mediate cellular differentiation in almost every type\\u000a of tissue including the retina (Murre et al. 1989; Jan and Jan 1993; Cepko 1999). Class A factors are ubiquitously expressed throughout mammalian tissue, while the expression\\u000a of class B factors are cell type specific. These factors have both a DNA binding domain and

Mark E. Pennesi; Debra E. Bramblett; Jang-Hyeon Cho; Ming-Jer Tsai; Samuel M. Wu

143

Notch and HES5 are regulated during human cartilage differentiation  

Microsoft Academic Search

The molecular mechanisms of cartilage differentiation are poorly understood. In a variety of tissues other than cartilage,\\u000a members of the basic helix-loop-helix (bHLH) family of transcription factors have been demonstrated to play critical roles\\u000a in differentiation. We have characterized the human bHLH gene HES5 and investigated its role during chondrogenesis. Blockage\\u000a of the Notch signaling pathway with a ?-secretase inhibitor

Camilla Karlsson; Marianne Jonsson; Julia Asp; Camilla Brantsing; Ryoichiro Kageyama; Anders Lindahl

2007-01-01

144

Expression of Neuro D1 in Human Normal Pituitaries and Pituitary Adenomas  

Microsoft Academic Search

Neuro D1 is a basic helix-loop-helix transcription factor expressed in the endocrine cells of pancreas and in a subset of neurons as they undergo terminal differentiation. In the adult pituitary gland, Neuro D1 is expressed in corticotroph cells and contributes to the corticotroph-specific pro-opiomelanocortin (POMC) transcription by interacting with Pituitary homeobox 1 (Ptx 1) transcription factor. In the present study,

Kenichi Oyama; Naoko Sanno; Akira Teramoto; R. Yoshiyuki Osamura

2001-01-01

145

Predisposition to Arrhythmia and Autonomic Dysfunction in Nhlh1Deficient Mice  

Microsoft Academic Search

Nhlh1 is a basic helix-loop-helix transcription factor whose expression is restricted to the nervous system and which may play a role in neuronal differentiation. To directly study Nhlh1 function, we generated null mice. Homozygous mutant mice were predisposed to premature, adult-onset, unexpected death. Electrocardiograms revealed decreased total heart rate variability, stress-induced arrhythmia, and impaired baroreceptor sensi- tivity. This predisposition to

Tiziana Cogliati; Deborah J. Good; Mark Haigney; Petra Delgado-Romero; Michael A. Eckhaus; Walter J. Koch; Ilan R. Kirsch

2002-01-01

146

Overexpression of Myogenin in Muscles of Transgenic Mice: Interaction with Id1, Negative Crossregulation of Myogenic Factors, and Induction of Extrasynaptic Acetylcholine Receptor Expression  

Microsoft Academic Search

To investigate the role of myogenin in regulating acetylcholine receptor expression in adult muscle, this muscle-specific basic helix-loop-helix transcription factor was overexpressed in transgenic mice by using regulatory elements conferring strong expression confined to differentiated postmitotic musclefibers. Many of the transgenic mice died during the first postnatal week, but those that survived into adulthood displayed normal muscle histology, gross morphology,

KRISTIAN GUNDERSEN; INGER RABBEN; BARBARA J. KLOCKE; ANDJOHN P. MERLIE

147

Drosophila Jing is part of the breathless fibroblast growth factor receptor positive feedback loop  

Microsoft Academic Search

In the developing Drosophila trachea, extensive cell migration lays the foundation for an elaborate network of tubules to form. This process is controlled\\u000a by the Drosophila fibroblast growth factor receptor, known as Breathless (Btl), whose expression is activated by the Trachealess (Trh) and\\u000a Tango (Tgo) basic helix-loop-helix (bHLH)-PAS transcription factors. We previously identified the jing zinc finger transcription factor as

Margaret Sonnenfeld; Tatiana Morozova; Joanne Hackett; Xuetao Sun

2010-01-01

148

A comparison of Twist and E-cadherin protein expression in primary non-small-cell lung carcinoma and corresponding metastases  

Microsoft Academic Search

Objective: The metastasis of solid tumors is directly or indirectly responsible for most cancer-related deaths. It has already been known that in non-small-cell lung carcinoma cells, up-regulation of Twist (a highly conserved basic helix-loop-helix transcription factor) can promote epithelial–mesenchymal transition through down-regulation of E-cadherin. The main aim of this study was to determine whether the expression of Twist and E-cadherin

Guanghui Wang; Wei Dong; Hongchang Shen; Xueru Mu; Zhenxiang Li; Xiaoyan Lin; Ying Liu; Jiajun Du

2011-01-01

149

The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter  

Microsoft Academic Search

Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired

Y Li; M Xie; J Yang; D Yang; R Deng; Y Wan; B Yan

2006-01-01

150

A New Turn (or Two) for Twist  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Two reports in this week's issue of Science [Baylies (p. 1481) and Spicer (p. 1476)] describe new functions in muscle development for the gene twist, a basic helix-loop-helix transcription factor. In his Perspective, Michelson explains how these two seemingly contradictory functions of twist (specification of mesodermal cell fate in fruit flies and inhibition of muscle differentiation in vertebrates) can be reconciled.

Alan M. Michelson (Brigham and Women's Hospital;Howard Hughes Medical Institute and the Department of Medicine)

1996-06-07

151

Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function  

Microsoft Academic Search

The Microphthalmia-associated transcription factor (Mitf) is required for the proper development of several cell lineages including osteoclasts, melanocytes, retinal pigment epithelial cells, mast cells and natural killer cells. Mutations in Mitf in multiple organisms result in osteopetrosis due to defective osteoclast development. Mitf is a member of the basic\\/helix-loop-helix\\/leucine zipper (b-HLH-ZIP) transcription factor subfamily named MiT, which also includes Tfe3.

Christine L Hershey; David E Fisher

2004-01-01

152

Multiple roles for the E\\/Daughterless ortholog HLH-2 during C. elegans gonadogenesis  

Microsoft Academic Search

HLH-2 is the Caenorhabditis elegans ortholog of the Drosophila Daughterless and mammalian E basic helix–loop–helix (bHLH) transcriptional activators that function during diverse events during animal development. HLH-2 has been implicated in cell fate specification in different neural lineages and in the LIN-12\\/Notch-mediated anchor cell (AC)\\/ventral uterine precursor cell (VU) decision in the somatic gonad. Here, we show that hlh-2 plays

Xantha Karp; Iva Greenwald

2004-01-01

153

Analysis of the Myc and Max Interaction Specificity with ? Repressor-HLH Domain Fusions  

Microsoft Academic Search

The basic helix-loop-helix domain (bHLH) is present in a large class of transcriptional regulators involved in developmental processes and oncogenesis. It determines DNA binding and specific homo- and heterodimeric protein associations, crucial for protein function. Myc and Max belong to a subset of HLH proteins, containing a leucine zipper (LZ) adjacent to the bHLH domain. They differ in dimerization and

Alessandra Marchetti; Marian Abril-Marti; Barbara Illi; Gianni Cesareni; Sergio Nasi

1995-01-01

154

Mammalian hairy and Enhancer of Split Homolog 1 Regulates Differentiation of Retinal Neurons and Is Essential for Eye Morphogenesis  

Microsoft Academic Search

Mammalian hairy and Enhancer of split homolog 1 (HES1), a basic helix-loop-helix factor gene, is expressed in retinal progenitor cells, and its expression decreases as differentiation proceeds. Retinal progenitor cells infected with HES1-transducing retrovirus did not differentiate into mature retinal cells, suggesting that persistent expression of HES1 blocks retinal development. In contrast, in the retina of HES1-null mutant mice, differentiation

Koichi Tomita; Makoto Ishibashi; Kiyoshi Nakahara; Siew-Lan Ang; Shigetada Nakanishi; François Guillemot; Ryoichiro Kageyama

1996-01-01

155

The myoD Gene Family: Nodal Point During Specification of the Muscle Cell Lineage  

Microsoft Academic Search

The myoD gene converts many differentiated cell types into muscle. MyoD is a member of the basic-helix-loophelix family of proteins; this 68-amino acid domain in MyoD is necessary and sufficient for myogenesis. MyoD binds cooperatively to muscle-specific enhancers and activates transcription. The helix-loop-helix motif is responsible for dimerization, and, depending on its dimerization partner, MyoD activity can be controlled. MyoD

Harold Weintraub; Robert Davis; Stephen Tapscott; Matthew Thayer; Michael Krause; Robert Benezra; T. Keith Blackwell; David Turner; Ralph Rupp; Stanley Hollenberg; Yuan Zhuang; Andrew Lassar

1991-01-01

156

A genomewide survey of developmentally relevant genes in Ciona intestinalis  

Microsoft Academic Search

The basic helix-loop-helix (bHLH) proteins are transcription factors that play important roles in many biological processes, including the development of various animals. We identified 46 genes encoding bHLH proteins in the draft genome sequence of the basal chordate Ciona intestinalis. These 46 genes represent an almost complete set of bHLH genes in this animal. This number is comparable to 39

Yutaka Satou; Kaoru S. Imai; Michael Levine; Yuji Kohara; Daniel Rokhsar; Nori Satoh

2003-01-01

157

The olig family: phylogenetic analysis and early gene expression in Xenopus tropicalis  

Microsoft Academic Search

The olig genes form a small subfamily of basic helix-loop-helix transcription factors. They were discovered in 2000 as genes required\\u000a for oligodendrocyte lineage specification. Since then, olig genes have been identified in various vertebrate species and corresponding sequences accumulated within genomic databases.\\u000a Until now, three groups of olig genes have been characterized. Our phylogenetic analysis demonstrates the existence of a

O. J. Bronchain; N. Pollet; Q. Ymlahi-Ouazzani; S. Dhorne-Pollet; J. C. Helbling; J. E. Lecarpentier; K. Percheron; M. Wegnez

2007-01-01

158

Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R)  

Microsoft Academic Search

Analysis of the nucleotide sequence of human melanocortin-1 receptor (MC1R) promoter indicated that an E-box (CANNTG) is present immediately upstream of the transcriptional initiation site. The presence of the CATGTG motif suggests that MC1R gene expression may be regulated by a basic helix-loop-helix-leucine-zipper (bHLH-LZ) type transcription factor. The microphthalmia-associated transcription factor (MITF), which belongs to the family of bHLH-LZ type

Hirofumi Aoki; Osamu Moro

2002-01-01

159

The highly conserved cardiogenic bHLH factor Hand is specifically expressed in circular visceral muscle progenitor cells and in all cell types of the dorsal vessel during Drosophila embryogenesis  

Microsoft Academic Search

. The highly conserved basic helix-loop-helix transcription factor Hand plays a crucial role in cardiogenesis, limb formation and other developmental processes of vertebrates. Humans, mice and other higher vertebrates have two related genes, dHand (also known as Hand2, Hed, Thing2) and eHand (also known as Hand1, Hxt, Thing1), whereas fish and Drosophila have only a single hand gene. We cloned

Verena Kölsch; Achim Paululat

2002-01-01

160

Anthocyanini of petunia controls pigment synthesis, vacuolar pH, and seed coat development by genetically distinct mechanisms  

Microsoft Academic Search

ANTHOCYANIN1 (AN1) of petunia is a transcription factor of the basic helix-loop-helix (bHLH) family that is required for the synthesis of anthocyanin pigments. Here, we show that AN1 controls additional aspects of cell differentiation: the acidification of vacuoles in petal cells, and the size and morphology of cells in the seed coat epidermis. We identified an1 alleles, formerly known as

Cornelis Spelt; Francesca Quattrocchio; Joseph Mol; Ronald Koes

2002-01-01

161

ASH1 Gene Is a Specific Therapeutic Target for Lung Cancers with Neuroendocrine Features  

Microsoft Academic Search

Lung cancers with neuroendocrine features are usually aggressive, although the underlying molecular mechanisms largely remain to be determined. The basic helix-loop-helix protein, achaete-scute complex-like 1\\/achaete-scute homo- logue 1 (ASH1), is expressed in normal fetal pulmonary neuroendocrine cells and lung cancers with neuroendocrine elements and is suggested to be involved in lung carcinogen- esis. In the present study, we show inhibition

Hirotaka Osada; Yoshio Tatematsu; Yasushi Yatabe; Yoshitsugu Horio; Takashi Takahashi

162

Id proteins expression in prostate cancer: high-level expression of Id4 in primary prostate cancer is associated with development of metastases  

Microsoft Academic Search

A major cause of treatment failure for prostate cancer is the development of androgen-independent metastatic disease. Id protein family, a group of basic helix–loop–helix transcription factors, has been shown to be involved in carcinogenesis and a prognostic marker in several types of human cancers. In this study, we examined the expressions of four Id proteins, Id-1, -2, -3 and -4,

Hiu-Fung Yuen; Chee-Wai Chua; Yuen-Piu Chan; Yong-Chuan Wong; Xianghong Wang; Kwok-Wah Chan

2006-01-01

163

Regulation of Skeletal Myogenesis by Association of the MEF2 Transcription Factor with Class II Histone Deacetylases  

Microsoft Academic Search

Skeletal muscle differentiation is controlled by associations between myogenic basic-helix-loop-helix and MEF2 transcription factors. We show that chromatin associated with muscle genes regulated by these transcription factors becomes acetylated during myogenesis and that class II histone deacetylases (HDACs), which interact with MEF2, specifically suppress myoblast differentiation. These HDACs do not interact directly with MyoD, yet they suppress its myogenic activity

Jianrong Lu; Timothy A. McKinsey; Chun-Li Zhang; Eric N. Olson

2000-01-01

164

Up-regulation of hypoxia-inducible factors HIF-1? and HIF-2? under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function  

Microsoft Academic Search

Hypoxia induces transcription of a range of physiologically important genes including erythropoietin and vascular endothelial growth factor. The transcriptional activation is mediated by the hypoxia-inducible factor-1 (HIF-1), a heterodimeric member of the basic helix–loop–helix PAS family, composed of ? and ? subunits. HIF-1? shares 48 per cent identity with the recently identified HIF-2? protein that is also stimulated by hypoxia.

Marion Krieg; Richard Haas; Hiltrud Brauch; Till Acker; Ingo Flamme; Karl H Plate

2000-01-01

165

Hes-6, an inhibitor of Hes-1, is regulated by 17?-estradiol and promotes breast cancer cell proliferation  

Microsoft Academic Search

Introduction  Hes-6 is a member of the basic helix-loop-helix (bHLH) family of transcription factors, and its overexpression has been reported\\u000a in metastatic cancers of different origins. Hes-6 has been described as an inhibitor of Hes-1 during neuronal development,\\u000a although its function in cancer is not known. In this study, we investigated the function of Hes-6 in breast cancer and tested\\u000a the

Johan Hartman; Eric W-F Lam; Jan-Åke Gustafsson; Anders Ström

2009-01-01

166

Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms  

Microsoft Academic Search

This article reviews the molecular structure, expression pattern, physiological function, pathological roles and molecular mechanisms of Twist1 in development, genetic disease and cancer. Twist1 is a basic helix-loop-helix domain-containing transcription factor. It forms homo- or hetero-dimers in order to bind the Nde1 E-box element and activate or repress its target genes. During development, Twist1 is essential for mesoderm specification and

Qian Qin; Young Xu; Tao He; Chunlin Qin; Jianming Xu

2012-01-01

167

PER and TIM Inhibit the DNA Binding Activity of a Drosophila CLOCK-CYC\\/dBMAL1 Heterodimer without Disrupting Formation of the Heterodimer: a Basis for Circadian Transcription  

Microsoft Academic Search

The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the circadian clock genes period (per) and timeless (tim). Several lines of evidence indicate that PER, TIM, or a PER-TIM heterodimer somehow inhibit the transcriptional activity of a

CHOOGON LEE; KIHO BAE; ISAAC EDERY

168

Functional Mapping of the Candida albicans Efg1 Regulator  

Microsoft Academic Search

Efg1p is a key transcriptional regulator in Candida albicans which controls various aspects of morphogenesis and metabolism in this organism. Efg1p contains a central basic helix-loop-helix (bHLH) domain, flanked by sequences highly conserved in fungal APSES proteins, as well as polyglutamine stretches at the N- and C-terminal ends. A systematic deletion approach to specify functional domains of Efg1p revealed that

Christine S. Noffz; Vanessa Liedschulte; Klaus Lengeler; Joachim F. Ernst

2008-01-01

169

Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor.  

PubMed Central

A cDNA encoding the murine Ah receptor (Ahb-1 allele for aromatic hydrocarbon responsiveness) has been isolated and characterized. Analysis of the deduced protein sequence revealed a region with similarity to the basic region/helix-loop-helix (BR/HLH) motif found in many transcription factors that undergo dimerization for function. In addition to the BR/HLH domain, the N-terminal domain of the Ah receptor has extensive sequence similarity to the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein and two regulatory proteins of Drosophila, Sim and Per. Photoaffinity labeling and peptide mapping studies indicate that the Ah receptor binds agonist at a domain that lies within this conserved N-terminal domain. The Ah receptor appears to be a ligand-activated transcription factor with a helix-loop-helix motif similar to those found in a variety of DNA-binding proteins, including Myc and MyoD. Images

Burbach, K M; Poland, A; Bradfield, C A

1992-01-01

170

Protein Mediators of Sterol Transport Across Intestinal Brush Border Membrane  

PubMed Central

Dysregulation of cholesterol balance contributes significantly to atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in the United States. The intestine has the unique capability to act as a gatekeeper for entry of cholesterol into the body, and inhibition of intestinal cholesterol absorption is now widely regarded as an attractive non-statin therapeutic strategy for ASCVD prevention. In this chapter we discuss the current state of knowledge regarding sterol transport across the intestinal brush border membrane. The purpose of this work is to summarize substantial progress made in the last decade in regards to protein-mediated sterol trafficking, and to discuss this in the context of human disease.

Brown, J. Mark; Yu, Liqing

2012-01-01

171

Morphology, Biophysical Properties and Protein-Mediated Fusion of Archaeosomes  

PubMed Central

As variance from standard phospholipids of eubacteria and eukaryotes, archaebacterial diether phospholipids contain branched alcohol chains (phytanol) linked to glycerol exclusively with ether bonds. Giant vesicles (GVs) constituted of different species of archaebacterial diether phospholipids and glycolipids (archaeosomes) were prepared by electroformation and observed under a phase contrast and/or fluorescence microscope. Archaebacterial lipids and different mixtures of archaebacterial and standard lipids formed GVs which were analysed for size, yield and ability to adhere to each other due to the mediating effects of certain plasma proteins. GVs constituted of different proportions of archaeal or standard phosphatidylcholine were compared. In nonarchaebacterial GVs (in form of multilamellar lipid vesicles, MLVs) the main transition was detected at Tm?=?34. 2°C with an enthalpy of ?H?=?0.68 kcal/mol, whereas in archaebacterial GVs (MLVs) we did not observe the main phase transition in the range between 10 and 70°C. GVs constituted of archaebacterial lipids were subject to attractive interaction mediated by beta 2 glycoprotein I and by heparin. The adhesion constant of beta 2 glycoprotein I – mediated adhesion determined from adhesion angle between adhered GVs was in the range of 10?8 J/m2. In the course of protein mediated adhesion, lateral segregation of the membrane components and presence of thin tubular membranous structures were observed. The ability of archaebacterial diether lipids to combine with standard lipids in bilayers and their compatibility with adhesion-mediating molecules offer further evidence that archaebacterial lipids are appropriate for the design of drug carriers.

Sustar, Vid; Zelko, Jasna; Lopalco, Patrizia; Lobasso, Simona; Ota, Ajda; Ulrih, Natasa Poklar; Corcelli, Angela; Kralj-Iglic, Veronika

2012-01-01

172

ATG proteins mediate efferocytosis and suppress inflammation in mammary involution.  

PubMed

Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1(+/-) and Atg7-deficient mammary epithelial cells (MECs) produced 'competent' apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment. Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance. PMID:23380905

Teplova, Irina; Lozy, Fred; Price, Sandy; Singh, Sukhwinder; Barnard, Nicola; Cardiff, Robert D; Birge, Raymond B; Karantza, Vassiliki

2013-04-01

173

Mammalian ORMDL Proteins Mediate the Feedback Response in Ceramide Biosynthesis*  

PubMed Central

The mammalian ORMDL proteins are orthologues of the yeast Orm proteins (Orm1/2), which are regulators of ceramide biosynthesis. In mammalian cells, ceramide is a proapoptotic signaling sphingolipid, but it is also an obligate precursor to essential higher order sphingolipids. Therefore levels of ceramide are expected to be tightly controlled. We tested the three ORMDL isoforms for their role in homeostatically regulating ceramide biosynthesis in mammalian cells. Treatment of cells with a short chain (C6) ceramide or sphingosine resulted in a dramatic inhibition of ceramide biosynthesis. This inhibition was almost completely eliminated by ORMDL knockdown. This establishes that the ORMDL proteins mediate the feedback regulation of ceramide biosynthesis in mammalian cells. The ORMDL proteins are functionally redundant. Knockdown of all three isoforms simultaneously was required to alleviate the sphingolipid-mediated inhibition of ceramide biosynthesis. The lipid sensed by the ORMDL-mediated feedback mechanism is medium or long chain ceramide or a higher order sphingolipid. Treatment of permeabilized cells with C6-ceramide resulted in ORMDL-mediated inhibition of the rate-limiting enzyme in sphingolipid biosynthesis, serine palmitoyltransferase. This indicates that C6-ceramide inhibition requires only membrane-bound elements and does not involve diffusible proteins or small molecules. We also tested the atypical sphingomyelin synthase isoform, SMSr, for its role in the regulation of ceramide biosynthesis. This unusual enzyme has been reported to regulate ceramide levels in the endoplasmic reticulum. We were unable to detect a role for SMSr in regulating ceramide biosynthesis. We suggest that the role of SMSr may be in the regulation of downstream metabolism of ceramide.

Siow, Deanna L.; Wattenberg, Binks W.

2012-01-01

174

ATG proteins mediate efferocytosis and suppress inflammation in mammary involution  

PubMed Central

Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1+/? and Atg7-deficient mammary epithelial cells (MECs) produced ‘competent’ apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment.   Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance.

Teplova, Irina; Lozy, Fred; Price, Sandy; Singh, Sukhwinder; Barnard, Nicola; Cardiff, Robert D.; Birge, Raymond B.; Karantza, Vassiliki

2013-01-01

175

Identification of a human achaete-scute homolog highly expressed in neuroendocrine tumors.  

PubMed Central

Basic helix-loop-helix transcription factors of the achaete-scute family are instrumental in Drosophila neurosensory development and are candidate regulators of development in the mammalian central nervous system and neural crest. We report the isolation and initial characterization of a human achaete-scute homolog that is highly expressed in two neuroendocrine cancers, medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). The human gene, which we have termed human achaete-scute homology 1 (hASH1), was cloned from a human MTC cDNA library. It encodes a predicted protein of 238 aa that is 95% homologous to mammalian achaete-scute homolog (MASH) 1, a rodent basic helix-loop-helix factor. The 57-residue basic helix-loop-helix domain is identical to that in the rodent gene, and the basic and helical regions, excluding the loop, are 72-80% identical to Drosophila achaete-scute family members. The proximal coding region of the hASH1 cDNA contains a striking 14-copy repeat of the triplet CAG that exhibits polymorphism in human genomic DNA. Thus, hASH1 is a candidate locus for disease-causing mutations via triplet repeat amplification. Analysis of rodent-human somatic cell hybrids permitted assignment of hASH1 to human chromosome 12. Northern blots revealed hASH1 transcripts in RNA from a human MTC cell line, two fresh MTC tumors, fetal brain, and three lines of human SCLC. In contrast, cultured lines of non-SCLC lung cancers and a panel of normal adult human tissues showed no detectable hASH1 transcripts. Expression of hASH1 may provide a useful marker for cancers with neuroendocrine features and may contribute to the differentiation and growth regulation of these cells. Images Fig. 3 Fig. 4 Fig. 5

Ball, D W; Azzoli, C G; Baylin, S B; Chi, D; Dou, S; Donis-Keller, H; Cumaraswamy, A; Borges, M; Nelkin, B D

1993-01-01

176

XATH-1,a Vertebrate Homolog of Drosophila atonal,Induces Neuronal Differentiation within Ectodermal Progenitors  

Microsoft Academic Search

XATH-1,a basic\\/helix-loop-helix transcription factor and a homolog ofDrosophila atonaland mammalianMATH-1,is expressed specifically in the dorsal hindbrain duringXenopusneural development. In order to investigate the role ofXATH-1in the neuronal differentiation process, we have examined the effects ofXATH-1overexpression duringXenopusdevelopment.XATH-1induces the expression of neuronal differentiation markers, such asN-tubulin,within the neural plate as well as within nonneural ectodermal progenitor populations, resulting in the appearance of

Peter Kim; Amy W. Helms; Jane E. Johnson; Kathryn Zimmerman

1997-01-01

177

A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis  

Microsoft Academic Search

Background and Aims  The aryl hydrocarbon receptor (AhR), which is a member of the basic helix-loop-helix\\/Per-Arnt-Sim homology superfamily, plays\\u000a an important role in multiple biological functions, and AhR knockout (AhR KO) animals suffer from a variety of organ disorders\\u000a including a decline in the efficacy of their immune system. In addition, AhR activation is known to aid the maintenance of\\u000a homeostasis

Keisuke FurumatsuShin; Shin Nishiumi; Yuki Kawano; Makoto Ooi; Tomoo Yoshie; Yuuki Shiomi; Hiromu Kutsumi; Hitoshi Ashida; Yoshiaki Fujii-Kuriyama; Takeshi Azuma; Masaru Yoshida

178

OVO homologue-like 1 ( Ovol1 ) transcription factor: a novel target of neurogenin-3 in rodent pancreas  

Microsoft Academic Search

Aims\\/hypothesis  The basic helix–loop–helix transcription factor neurogenin-3 (NGN3) commits the fates of pancreatic progenitors to endocrine\\u000a cell types, but knowledge of the mechanisms regulating the choice between proliferation and differentiation of these progenitors\\u000a is limited.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Using a chromatin immunoprecipitation cloning approach, we searched for direct targets of NGN3 and identified a zinc-finger\\u000a transcription factor, OVO homologue-like 1 (OVOL1). Transactivation experiments were

A. Vetere; W.-C. Li; F. Paroni; K. Juhl; L. Guo; W. Nishimura; X. Dai; S. Bonner-Weir; A. Sharma

2010-01-01

179

Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max  

Microsoft Academic Search

THE c-myc protein (Myc) contains an amino-terminal transcriptional activation domain1 and a carboxy-terminal basic helix-loop-helix-leucine zipper (bHLH-Z) domain2-5 that directs dimerization of Myc with its partner, the max protein (Max), and promotes DNA binding to sites containing a CACGTG core consensus sequence6-9. Despite these characteristics and the observation that Myc can modulate gene expression4,5,10, a direct role for Myc or

Bruno Amati; Stephen Dalton; Mary W. Brooks; Trevor D. Littlewood; Gerard I. Evan; Hartmut Land

1992-01-01

180

In silico cloning and characterization of p8 homolog cDNA from common urchin ( Paracentrotus lividus )  

Microsoft Academic Search

The p8 protein is a transcription factor with a basic helix-loop-helix motif and a nuclear localization signal. In the present\\u000a study, a common sea urchin (Paracentrotus lividus) homolog of p8 cDNA was cloned, sequenced and characterized. The full-length p8 cDNA consists of 896 bp and encodes 71 amino\\u000a acids with a molecular mass of 8.238 kD. Homology alignments found that several phosphorylation

Jia-Qing Wang; Jin-Cheng Han; Dai-Zong Li; Lin-Chun Li

2009-01-01

181

The role of Atonal transcription factors in the development of mechanosensitive cells  

PubMed Central

Mechanosensation is an evolutionarily ancient sensory modality seen in allmain animal groups. Mechanosensation can be mediated by sensory neurons or by dedicated receptor cells that form synapses with sensory neurons. Evidence over the last 15–20 years suggests that both classes of mechanosensory cells can be specified by the atonal class of basic helix-loop-helix transcription factors. In this review we discuss recent work addressing how atonal factors specify mechanosensitive cells in vertebrates and invertebrates, and how the redeployment of these factors underlies the regeneration of mechanosensitive cells in some vertebrate groups.

Jarman, Andrew P.; Groves, Andrew K.

2013-01-01

182

Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways.  

PubMed

E47 is a basic helix-loop-helix transcription factor involved in neuronal differentiation and survival. We had previously shown that the basic helix-loop-helix protein E47 binds to E-box sequences within the promoter of the TrkB gene and activates its transcription. Proper expression of the TrkB receptor plays a key role in development and function of the vertebrate nervous system, and altered levels of TrkB have been associated with important human diseases. Here we show that E47 interacts with MLK2, a mixed lineage kinase (MLK) involved in JNK-mediated activation of programmed cell death. MLK2 enhances phosphorylation of the AD2 activation domain of E47 in vivo in a JNK-independent manner and phosphorylates in vitro defined serine and threonine residues within a loop-helix structure of AD2 that also contains a putative MLK docking site. Although these residues are essential for MLK2-mediated inactivation of E47, inhibition of MLKs by CEP11004 causes up-regulation of TrkB at a transcriptional level in cerebellar granule neurons and differentiating neuroblastoma cells. These findings allow us to propose a novel mechanism by which MLK regulates TrkB expression through phosphorylation of an activation domain of E47. This molecular link would explain why MLK inhibitors not only prevent activation of cell death processes but also enhance cell survival signaling as a key aspect of their neuroprotective potential. PMID:19801649

Pedraza, Neus; Rafel, Marta; Navarro, Isis; Encinas, Mario; Aldea, Martí; Gallego, Carme

2009-11-20

183

The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis.  

PubMed

Myogenesis is regulated by the basic helix-loop-helix (bHLH) myogenic regulatory factor MyoD, which induces muscle-specific gene expression by binding to the E-box sequence as a heterodimer with ubiquitous bHLH E2A (E12/E47) proteins. Here, we report that a 31-kDa caspase-generated cleavage product of Crk-associated substrate (p130Cas), herein called 31-kDa, is downregulated during muscle cell differentiation. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id (inhibitor of DNA binding) proteins than with bHLH proteins. This HLH domain, lacking the basic region required for DNA binding, mediated the direct interaction of 31-kDa with MyoD. Overexpression of 31-kDa in C3H10T1/2 cells inhibited not only the transcriptional activation of p21(Waf1/Cip1) and E-box-dependent muscle-specific genes by MyoD and/or E2A but also MyoD-induced myosin heavy chain expression and myogenic conversion. In sum, our results suggest a role for 31-kDa as a negative regulator of MyoD in the muscle differentiation program. PMID:24472550

Jeong, Da Eun; Lee, Eun Kyung; Song, Woo Keun; Kim, Wook

2014-02-21

184

PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) regulates auxin biosynthesis at high temperature  

PubMed Central

At high ambient temperature, plants display dramatic stem elongation in an adaptive response to heat. This response is mediated by elevated levels of the phytohormone auxin and requires auxin biosynthesis, signaling, and transport pathways. The mechanisms by which higher temperature results in greater auxin accumulation are unknown, however. A basic helix-loop-helix transcription factor, PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), is also required for hypocotyl elongation in response to high temperature. PIF4 also acts redundantly with its homolog, PIF5, to regulate diurnal growth rhythms and elongation responses to the threat of vegetative shade. PIF4 activity is reportedly limited in part by binding to both the basic helix-loop-helix protein LONG HYPOCOTYL IN FAR RED 1 and the DELLA family of growth-repressing proteins. Despite the importance of PIF4 in integrating multiple environmental signals, the mechanisms by which PIF4 controls growth are unknown. Here we demonstrate that PIF4 regulates levels of auxin and the expression of key auxin biosynthesis genes at high temperature. We also identify a family of SMALL AUXIN UP RNA (SAUR) genes that are expressed at high temperature in a PIF4-dependent manner and promote elongation growth. Taken together, our results demonstrate direct molecular links among PIF4, auxin, and elongation growth at high temperature.

Franklin, Keara A.; Lee, Sang Ho; Patel, Dhaval; Kumar, S. Vinod; Spartz, Angela K.; Gu, Chen; Ye, Songqing; Yu, Peng; Breen, Gordon; Cohen, Jerry D.; Wigge, Philip A.; Gray, William M.

2011-01-01

185

Achaete-scute homologue-1 (ASH1) stimulates migration of lung cancer cells through Cdk5/p35 pathway  

PubMed Central

Our previous data suggested that the human basic helix–loop–helix transcription factor achaete-scute homologue-1 (hASH1) may stimulate both proliferation and migration in the lung. In the CNS, cyclin-dependent kinase 5 (Cdk5) and its activator p35 are important for neuronal migration that is regulated by basic helix–loop–helix transcription factors. Cdk5/p35 may also play a role in carcinogenesis. In this study, we found that the neuronal activator p35 was commonly expressed in primary human lung cancers. Cdk5 and p35 were also expressed by several human lung cancer cell lines and coupled with migration and invasion. When the kinase activity was inhibited by the Cdk5 inhibitor roscovitine or dominant-negative (dn) Cdk5, the migration of lung cancer cells was reduced. In neuroendocrine cells expressing hASH1, such as a pulmonary carcinoid cell line, knocking down the gene expression by short hairpin RNA reduced the levels of Cdk5/p35, nuclear p35 protein, and migration. Furthermore, expression of hASH1 in lung adenocarcinoma cells normally lacking hASH1 increased p35/Cdk5 activity and enhanced cellular migration. We were also able to show that p35 was a direct target for hASH1. In conclusion, induction of Cdk5 activity is a novel mechanism through which hASH1 may regulate migration in lung carcinogenesis.

Demelash, Abeba; Rudrabhatla, Parvathi; Pant, Harish C.; Wang, Xiaoyang; Amin, Niranjana D.; McWhite, Claire D.; Naizhen, Xu; Linnoila, R. Ilona

2012-01-01

186

A dominant-negative mutant of Max that inhibits sequence-specific DNA binding by Myc proteins.  

PubMed Central

Myc proteins are basic helix-loop-helix/leucine-zipper proteins that bind to specific DNA sequences. In vivo, Myc proteins have been found associated with Max, another basic helix-loop-helix/leucine-zipper protein. However, it is not known to what extent the dimerization of Myc with Max is required for the manifestation of the Myc-induced phenotype. To investigate this, we constructed a dominant-negative mutant of Max, named dMax, that inhibits sequence-specific DNA binding of Myc proteins. Using a rat neuroblastoma model system, we show that dMax reverts N-Myc-induced changes in cellular gene expression. A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression. These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7

Billaud, M; Isselbacher, K J; Bernards, R

1993-01-01

187

Mechanisms and Regulation of Protein-Mediated Cellular Fatty Acid Uptake: Molecular, Biochemical, and Physiological Evidence  

NSDL National Science Digital Library

In recent years, there has been considerable debate as to whether fatty acid is transported into cells or diffuses rapidly into the cell. It now appears that this debate is less strident, as it has been acknowledged recently that evidence supporting passive diffusion as the main mechanism for fatty acid uptake is apparently in error, since "previous reports for rapid flip-flop were based on an incorrect interpretation of the measurements" (79), Because of this (79) and other experiments (78), it has been concluded that "the lipid bilayer portion of biological membranes may present a significant barrier to transport of FFA across cell membranes" (36) and that "flip-flop is the rate limiting step for FFA transport across lipid vesicles" (78). Furthermore, "this implies that at least certain biological membranes may require protein-mediated transporters to catalyze the flip-flop step" (78). Since we (13, 27ÃÂ29, 73, 97, 98, 100) and others (32, 45, 54) have previously provided considerable support for the protein-mediated entry of long-chain fatty acids into the cell, especially in metabolically important tissues such as heart and skeletal muscle, we concur with these recent conclusions (36, 78, 79) that (membrane-associated) proteins are involved in cellular fatty acid uptake.

2007-02-01

188

MAP Kinases have different functions in Dictyostelium G Protein-Mediated Signaling  

PubMed Central

Extracellular signal regulated kinases (ERKs) are a class of MAP kinases that function in many signaling pathways in eukaryotic cells and in some cases, a single stimulus can activate more than one ERK suggesting functional redundancy or divergence from a common pathway. Dictyostelium discoideum encodes only two MAP kinases, ERK1 and ERK2, that both function during the developmental life cycle. To determine if ERK1 and ERK2 have overlapping functions, chemotactic and developmental phenotypes of erk1? and erk2? mutants were assessed with respect to G protein-mediated signal transduction pathways. ERK1 was specifically required for G?5-mediated tip morphogenesis and inhibition of folate chemotaxis but not for cAMP-stimulated chemotaxis or cGMP accumulation. ERK2 was the primary MAPK phosphorylated in response to folate or cAMP stimulation. Cell growth was not altered in erk1?, erk2? or erk1?erk2? mutants but each mutant displayed a different pattern of cell sorting in chimeric aggregates. The distribution of GFP-ERK1 or GFP-ERK2 fusion proteins in the cytoplasm and nucleus was not grossly altered in cells stimulated with cAMP or folate. These results suggest ERK1 and ERK2 have different roles in G protein-mediated signaling during growth and development.

Nguyen, Hoai-Nghia; Raisley, Brent; Hadwiger, Jeffrey A.

2010-01-01

189

Inhibitor of DNA Binding 4 (ID4) Regulation of Adipocyte Differentiation and Adipose Tissue Formation in Mice*  

PubMed Central

Inhibitor of DNA binding 4 (ID4) is a helix-loop-helix protein that heterodimerizes with basic helix-loop-helix transcription factors inhibiting their function. ID4 expression is important for adipogenic differentiation of the 3T3-L1 cell line, and inhibition of ID4 is associated with a concomitant decrease in CCAAT/enhancer-binding protein ? and peroxisome proliferator-activated receptor ? mRNA and protein expression. Mice with a homozygous deletion of Id4 (Id4?/?) have reduced body fat and gain much less weight compared with wild-type littermates when placed on diets with high fat content. Mouse embryonic fibroblasts (MEFs) isolated from Id4?/? mice have reduced adipogenic potential when compared with wild-type MEFs. In agreement with changes in morphological differentiation, the levels of CCAAT/enhancer-binding protein ? and peroxisome proliferator-activated receptor ? were also reduced in MEFs from Id4?/? mice. Our results demonstrate the importance of ID4 in adipocyte differentiation and the implications of this regulation for adipose tissue formation.

Murad, Joana M.; Place, Chelsea S.; Ran, Cong; Hekmatyar, Shahryar K. N.; Watson, Nathan P.; Kauppinen, Risto A.; Israel, Mark A.

2010-01-01

190

What's Basic About Basic Emotions?  

Microsoft Academic Search

A widespread assumption in theories of emotion is that there exists a small set of basic emotions. From a biological perspective, this idea is manifested in the belief that there might be neurophysiological and anatomical substrates corresponding to the basic emotions. From a psychological perspective, basic emotions are often held to be the primitive building blocks of other, nonbasic emotions.

Andrew Ortony; Terence J. Turner

1990-01-01

191

HaloTag protein-mediated specific labeling of living cells with quantum dots.  

PubMed

Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging. PMID:18621022

So, Min-kyung; Yao, Hequan; Rao, Jianghong

2008-09-26

192

HaloTag protein-mediated specific labeling of living cells with quantum dots  

SciTech Connect

Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging.

So, Min-kyung; Yao Hequan [Biophysics, Cancer Biology, and Molecular Imaging Programs, Department of Radiology, Stanford University School of Medicine, 1201 Welch Road, P093, Mail code 5484, Stanford, CA 94305 (United States); Rao Jianghong [Biophysics, Cancer Biology, and Molecular Imaging Programs, Department of Radiology, Stanford University School of Medicine, 1201 Welch Road, P093, Mail code 5484, Stanford, CA 94305 (United States)], E-mail: jrao@stanford.edu

2008-09-26

193

Corrosion Basics  

SciTech Connect

Retaining much of the text of the Basic Corrosion Course, Corrosion Basics contains updated, and additional information on plastics, concrete, coatings, water, cracking phenomena, and design. Chapters were rearranged. The cross referenced index was retained and updated to facilitate the quick location of any topic throughout the text. This publication provides the general coverage of the field of corrosion.

Not Available

1985-01-01

194

Basic HTML  

NSDL National Science Digital Library

Although most web designers use an editor, it is a good idea to have a working knowledge of HTML code. It is useful to be able to go into the code and make adjustments that an editor will not do. knowing HTML will give you more control over the look and function of your web site. Remember that this is just the basics but will provide you with the tools to design great web sites. Assignment Instructions: Go through the HTML Goodies Primers. You will create some basic web pages in these primers. E-mail your instructor each primer assignment at tami.warnick@cmacademy.org Primer 1: Basic HTML: Introduction Instructions: Read through the primer and then send your instructor a breif summary of what you learned. Primer 2: Learn the Basic HTML Tags! Instructions: After ...

Warnick, Mrs.

2009-12-04

195

The Basics  

ERIC Educational Resources Information Center

These articles are presented as an aide in teaching basic subjects. This issue examines reading diagnosis, food preservation, prime numbers, electromagnets, acting out in language arts, self-directed spelling activities, and resources for environmental education. (Editor/RK)

Indrisano, Roselmina; And Others

1976-01-01

196

Dispersion Basics  

NSDL National Science Digital Library

In this Webcast, Dr. Timothy Spangler (Director of the COMET Program and a former air quality consultant) provides a brief overview of the basics of atmospheric dispersion and how dispersion is modeled, particularly for accidental releases of hazardous materials. The lecture is presented in six sections and covers the effects of stability, turbulence, plume rise, and wind. Basic dispersion models are discussed, along with a brief summary of models used in special situations and factors that complicate their use.

Spangler, Tim

2002-11-01

197

Refractive-Index-Based Screening of Membrane-Protein-Mediated Transfer across Biological Membranes  

PubMed Central

Abstract Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore.

Branden, Magnus; Tabaei, Seyed R.; Fischer, Gerhard; Neutze, Richard; Hook, Fredrik

2010-01-01

198

The respiratory syncytial virus (RSV) nonstructural proteins mediate RSV suppression of glucocorticoid receptor transactivation.  

PubMed

Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is not responsive to glucocorticoids. We have shown that RSV infection impairs glucocorticoid receptor (GR) function. In this study, we have investigated the mechanism by which RSV impairs GR function. We have shown that RSV repression of GR-induced transactivation is not mediated through a soluble autocrine factor. Knock-down of mitochondrial antiviral signaling protein (MAVS), but not retinoic acid-inducible gene 1 (RIG-I) or myeloid differentiation primary response gene 88 (MyD88), impairs GR-mediated gene activation even in mock-infected cells. Over-expression of the RSV nonstructural protein NS1, but not NS2, impairs glucocorticoid-induced transactivation and viruses deleted in NS1 and/or NS2 are unable to repress glucocorticoid-induction of the known GR regulated gene glucocorticoid-inducible leucine zipper (GILZ). These data suggest that the RSV nonstructural proteins mediate RSV repression of GR-induced transactivation and that inhibition of the nonstructural proteins may be a viable target for therapy against RSV-related disease. PMID:24418538

Webster Marketon, Jeanette I; Corry, Jacqueline; Teng, Michael N

2014-01-20

199

Coat-protein-mediated resistance to tobacco mosaic virus: discovery mechanisms and exploitation.  

PubMed Central

In 1986 we reported that transgenic plants which accumulate the coat protein of tobacco mosaic virus (TMV) are protected from infection by TMV, and by closely related tobamoviruses. The phenomenon is referred to as coat-protein-mediated resistance (CP-MR), and bears certain similarities to cross protection, a phenomenon described by plant pathologists early in this century. Our studies of CP-MR against TMV have demonstrated that transgenically expressed CP interferes with disassembly of TMV particles in the inoculated transgenic cell. However, there is little resistance to local, cell-to-cell spread of infection. CP-MR involves interaction between the transgenic CP and the CP of the challenge virus, and resistance to TMV is greater than to tobamo viruses that have CP genes more distantly related to the transgene. Using the known coordinates of the three-dimensional structure of TMV we developed mutant forms of CP that have stronger inter-subunit interactions, and confer increased levels of CP-MR compared with wild-type CP. Similarly, it is predicted that understanding the cellular and structural basis of CP-MR will lead to the development of variant CP transgenes that each can confer high levels of resistance against a range of tobamoviruses.

Beachy, R N

1999-01-01

200

Identification of bacterial proteins mediating the interactions between Pseudomonas putida UW4 and Brassica napus (Canola).  

PubMed

The influence of canola root exudates on the proteome of Pseudomonas putida UW4 and the mutant strain P. putida UW4/AcdS(-), which lacks a functional 1-aminocyclopropane-1-carboxylate deaminase gene, was examined using two-dimensional difference in-gel electrophoresis. Seventy-two proteins with significantly altered expression levels in the presence of canola root exudates were identified by mass spectrometry. Many of these proteins are involved in nutrient transport and utilization, cell envelope synthesis, and transcriptional or translational regulation and, hence, may play important roles in plant-bacterial interactions. Four proteins showing large changes in expression in response to canola root exudates in both the wild-type and mutant strains of P. putida UW4 (i.e., outer membrane protein F, peptide deformylase, transcription regulator Fis family protein, and a previously uncharacterized protein) were both overexpressed and disrupted in P. putida UW4 in an effort to better understand their functions. Functional studies of these modified strains revealed significantly enhanced or inhibited plant-growth-promoting abilities compared with the wild-type P. putida UW4, in agreement with the suggested involvement of three of these four proteins in plant-bacterial interactions. The work reported here suggests strategies to both identify potential antibacterial agents and develop bacterial strains that might be useful adjuncts to agriculture. This approach may be an effective means of identifying key proteins mediating the interactions of bacteria with their rhizosphere environment. PMID:19445593

Cheng, Zhenyu; Duan, Jin; Hao, Youai; McConkey, Brendan J; Glick, Bernard R

2009-06-01

201

DOS basics  

SciTech Connect

DOS is an acronym for Disk Operating System. It is actually a set of programs that allows you to control your personal computer. DOS offers the capabilities to create and manage files; organize and maintain information placed on disks; use application programs such as WordPerfect, Lotus 123, Excel, Windows, etc. In addition, DOS provides the basic utilities needed to copy files from one area to another, delete files and list files. The latest version of DOS also offers more advanced features that include hard disk compression and memory management. Basic DOS commands are discussed.

O`Connor, P.

1994-09-01

202

Specific conformational epitope features of pathogenesis-related proteins mediating cross-reactivity between pollen and food allergens  

Microsoft Academic Search

Selected members of plant pathogenesis-related and seed storage proteins represent specific groups of proteins with potential\\u000a characteristics of allergens. Efforts to understand the mechanism by which pathogenesis-related proteins mediate a broad cross-reactivity\\u000a in pollen-plant food allergens are still limited. In this study, computational biology approach was used to reveal specific\\u000a structural implications and conservation of different epitopes from members of

Jose C. Jimenez-Lopez; Emma W. Gachomo; Oluwole A. Ariyo; Lamine Baba-Moussa; Simeon O. Kotchoni

203

Weather Basics  

NSDL National Science Digital Library

Students are introduced to the basics of the Earth's weather. Concepts include fundamental causes of common weather phenomena such as temperature changes, wind, clouds, rain and snow. The different factors that affect the weather and the instruments that measure weather data are also addressed.

Integrated Teaching And Learning Program

204

Basic Horticulture.  

ERIC Educational Resources Information Center

This learning packet contains teaching suggestions and student learning materials for a course in basic horticulture aimed at preparing students for employment in a number of horticulture areas. The packet includes nine sections and twenty instructional units. Following the standard format established for Oklahoma vocational education materials in…

Geer, Barbra Farabough

205

Basic Science.  

ERIC Educational Resources Information Center

Instructional materials are provided for a course that covers basic concepts of physics and chemistry. Designed for use in a workplace literacy project developed by Mercer County Community College (New Jersey) and its partners, the course describes applications of these concepts to real-life situations, with an emphasis on applications of…

Mercer County Community Coll., Trenton, NJ.

206

Protein-Mediated Antagonism between HIV Reverse Transcriptase Ligands Nevirapine and MgATP  

PubMed Central

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT.

Zheng, Xunhai; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.

2013-01-01

207

Effect of Reactor Turbulence on the Binding-Protein-Mediated Aspartate Transport System in Thin Wastewater Biofilms  

PubMed Central

This research documents an effect of reactor turbulence on the ability of gram-negative wastewater biofilm bacteria to actively transport l-aspartate via a binding-protein-mediated transport system. Biofilms which were not preadapted to turbulence and which possessed two separate and distinct aspartate transport systems (systems 1 and 2) were subjected to a turbulent flow condition in a hydrodynamically defined closed-loop reactor system. A shear stress treatment of 3.1 N · m?2 for 10 min at a turbulent Reynolds number (Re = 11,297) inactivated the low-affinity, high-capacity binding-protein-mediated transport system (system 2) and resolved the high-affinity, low-capacity membrane-bound proton symport system (system 1). The Kt and Vmax values for the resolved system were statistically similar to Kt and Vmax values for system 1 when system 2 was inactivated either by osmotic shock or arsenate, two treatments which are known to inactivate binding-protein-mediated transport systems. We hypothesize that shear stress disrupts system 2 by deforming the outer membranes of the firmly adhered gram-negative bacteria.

Eighmy, T. Taylor; Bishop, P. L.

1985-01-01

208

Tremor (Beyond the Basics)  

MedlinePLUS

... of Parkinson disease Overview of tremor Patient information: Fragile X syndrome (The Basics) Patient information: Myoclonus (The Basics) Patient ... Basics) Patient information: Myoclonus (The Basics) Patient information: Fragile X syndrome (The Basics) Beyond the Basics — Beyond the Basics ...

209

Contour Basics  

NSDL National Science Digital Library

Contour Basics is an exercise designed to introduce students to contour plots. The Contour Activity is a great on-line resource that starts slowly and increases in difficulty. It teaches students basic techniques for generating contours, introduces students to the subtleties of generating contour plots with sparse data, provides many opportunities for students to assess their own progress and understanding and has complete on-line drawing capabilities. The exercise is geared toward atmospheric and oceanic sciences but is beneficial for all geoscience students. In addition to the exercise, this site includes information on teaching materials, teaching notes and tips, assessment suggestions and additional references. This activity is part of the Starting Point Collection: http://serc.carleton.edu/introgeo/

Ackerman, Steve; Mackay, R. M.; Whittaker, Tom

2011-05-12

210

Basic Immunology  

NSDL National Science Digital Library

Some individuals might blanch at the idea of a "basic" immunology overview, but Professor Vladimir V. Klimov provides just such a resource on this site. As the homepage notes, the site is designed to assist undergraduate students learning about the basics of immunology through essays, images, animations, quizzes, case histories, and external links. Visitors can begin by looking over the "Table of Contents" area, which includes seven complete chapters of information. These chapters include "The Immune Responses", "Effector Activity", and "Functional Organization of the Immune System". While some of the materials on the site require a paid subscription, there's enough free material here to get students on their way to learning more about this field of study.

Klimov, Vladimir V.

211

Education: The Basics. The Basics  

ERIC Educational Resources Information Center

Everyone knows that education is important, we are confronted daily by discussion of it in the media and by politicians, but how much do we really know about education? "Education: The Basics" is a lively and engaging introduction to education as an academic subject, taking into account both theory and practice. Covering the schooling system, the…

Wood, Kay

2011-01-01

212

Poly(rC) binding proteins mediate poliovirus mRNA stability.  

PubMed Central

The 5'-terminal 88 nt of poliovirus RNA fold into a cloverleaf RNA structure and form ribonucleoprotein complexes with poly(rC) binding proteins (PCBPs; AV Gamarnik, R Andino, RNA, 1997, 3:882-892; TB Parsley, JS Towner, LB Blyn, E Ehrenfeld, BL Semler, RNA, 1997, 3:1124-1134). To determine the functional role of these ribonucleoprotein complexes in poliovirus replication, HeLa S10 translation-replication reactions were used to quantitatively assay poliovirus mRNA stability, poliovirus mRNA translation, and poliovirus negative-strand RNA synthesis. Ribohomopoly(C) RNA competitor rendered wild-type poliovirus mRNA unstable in these reactions. A 5'-terminal 7-methylguanosine cap prevented the degradation of wild-type poliovirus mRNA in the presence of ribohomopoly(C) competitor. Ribohomopoly(A), -(G), and -(U) did not adversely affect poliovirus mRNA stability. Ribohomopoly(C) competitor RNA inhibited the translation of poliovirus mRNA but did not inhibit poliovirus negative-strand RNA synthesis when poliovirus replication proteins were provided in trans using a chimeric helper mRNA possessing the hepatitis C virus IRES. A C24A mutation prevented UV crosslinking of PCBPs to 5' cloverleaf RNA and rendered poliovirus mRNA unstable. A 5'-terminal 7-methylguanosine cap blocked the degradation of C24A mutant poliovirus mRNA. The C24A mutation did not inhibit the translation of poliovirus mRNA nor diminish viral negative-strand RNA synthesis relative to wild-type RNA. These data support the conclusion that poly(rC) binding protein(s) mediate the stability of poliovirus mRNA by binding to the 5'-terminal cloverleaf structure of poliovirus mRNA. Because of the general conservation of 5' cloverleaf RNA sequences among picornaviruses, including C24 in loop b of the cloverleaf, we suggest that viral mRNA stability of polioviruses, coxsackieviruses, echoviruses, and rhinoviruses is mediated by interactions between PCBPs and 5' cloverleaf RNA.

Murray, K E; Roberts, A W; Barton, D J

2001-01-01

213

GPS Basics  

NSDL National Science Digital Library

The Federal Aviation Administration maintains the graphically impressive Global Positioning System (GPS) Basics Web site. From the history of the global positioning system and how it works to governmental policy that controls its use, this site does a good job of explaining all facets of what GPS is about without being overly technical. Interested visitors can explore some of the other links that cover satellite navigation topics as well, such as GPS programs; a library of documents, fact sheets, press releases, and news; frequently asked questions; links; and more. Anyone interested in mapping, navigation, or similar subjects will enjoy exploring the interesting information provided on this well designed site.

214

Basically Acids  

NSDL National Science Digital Library

Students learn the basics of acid/base chemistry in a fun, interactive way by studying instances of acid/base chemistry found in popular films such as Harry Potter and the Prisoner of Azkaban and National Treasure. Students learn what acids, bases and indicators are and how they can be used, including invisible ink. They also learn how engineers use acids and bases every day to better our quality of life. Students' interest is piqued by the use of popular culture in the classroom.

University Of Houston

215

Sunspace basics  

SciTech Connect

Anyone who lives in a home with a sunspace will tell you that the sunspace is the most enjoyable room in the house. Many times the homeowner`s only regret is that the sunspace is not larger. Although aesthetics often drive the decision to add a sunspace or include one in a new home design, sunspaces can also provide supplemental space heating and a healthy environment for plants and people. In fact, a well-designed sunspace can provide up to 60% of a home`s winter heating requirements. This publication addresses basic elements of sunspace design; design considerations for supplemental space heating, growing plants, and use as a living space; design guidelines including siting, heat distribution, and glazing angles; and major sunspace components including glazing options, thermal mass, insulation, and climate controls. A list of sources for more information is also provided.

Not Available

1994-11-01

216

Barometer Basics  

NSDL National Science Digital Library

This experimental activity is designed to develop a basic understanding of the interrelationship between temperature and pressure and the structure of a device made to examine this relationship. Resources needed to conduct this activity include two canning jars, two large rubber balloons, a heat lamp or lamp with 150 watt bulb, and access to freezer or water and ice. The resource includes background information, teaching tips and questions to guide student discussion. This is chapter 5 of Meteorology: An Educator's Resource for Inquiry-Based Learning for Grades 5-9. The guide includes a discussion of learning science, the use of inquiry in the classroom, instructions for making simple weather instruments, and more than 20 weather investigations ranging from teacher-centered to guided and open inquiry investigations.

217

RNA-binding protein-mediated post-transcriptional controls of gene expression: Integration of molecular mechanisms at the 3' end of mRNAs?  

PubMed

Initially identified as an occasional and peculiar mode of gene regulation in eukaryotes, RNA-binding protein-mediated post-transcriptional control of gene expression has emerged, over the last two decades, as a major contributor in the control of gene expression. A large variety of RNA-binding proteins (RBPs) allows the recognition of very diverse messenger RNA sequences and participates in the regulation of basically all cellular processes. Nevertheless, the rapid outcome of post-transcriptional regulations on the level of gene expression has favored the expansion of this type of regulation in cellular processes prone to rapid and frequent modulations such as the control of the inflammatory response. At the molecular level, the 3'untranslated region (3'UTR) of mRNA is a favored site of RBP recruitment. RBPs binding to these regions control gene expression through two major modes of regulation, namely mRNA decay and modulation of translational activity. Recent progresses suggest that these two mechanisms are often interdependent and might result one from the other. Therefore, different RBPs binding distinct RNA subsets could share similar modes of action at the molecular level. RBPs are frequent targets of post-translational modifications, thereby disclosing numerous possibilities for pharmacological interventions. However, redundancies of the transduction pathways controlling these modifications have limited the perspectives to define RBPs as new therapeutic targets. Through the analysis of several examples of RBPs binding to 3'Untranslated Region of mRNA, we present here recent progress and perspectives regarding this rapidly evolving field of molecular biology. PMID:24735612

Vindry, Caroline; Vo Ngoc, Long; Kruys, Véronique; Gueydan, Cyril

2014-06-15

218

Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis.  

PubMed

The MiTF/TFE family of basic helix-loop-helix leucine zipper transcription factors includes MITF, TFEB, TFE3, and TFEC. The involvement of some family members in the development and proliferation of specific cell types, such as mast cells, osteoclasts, and melanocytes, is well established. Notably, recent evidence suggests that the MiTF/TFE family plays a critical role in organelle biogenesis, nutrient sensing, and energy metabolism. The MiTF/TFE family is also implicated in human disease. Mutations or aberrant expression of most MiTF/TFE family members has been linked to different types of cancer. At the same time, they have recently emerged as novel and very promising targets for the treatment of neurological and lysosomal diseases. The characterization of this fascinating family of transcription factors is greatly expanding our understanding of how cells synchronize environmental signals, such as nutrient availability, with gene expression, energy production, and cellular homeostasis. PMID:24477476

Martina, José A; Diab, Heba I; Li, Huiqing; Puertollano, Rosa

2014-07-01

219

Functional Interconnection of MYC2 and SPA1 in the Photomorphogenic Seedling Development of Arabidopsis1  

PubMed Central

MYC2 is a basic helix-loop-helix transcription factor that cross talks with light, abscisic acid (ABA), and jasmonic acid (JA) signaling pathways. Here, we have shown that Arabidopsis (Arabidopsis thaliana) MYC2 directly binds to the G-box present in the SUPPRESSOR OF PHYTOCHROME A1 (SPA1) promoter and that it controls the expression of SPA1 in a COP1-dependent manner. Analyses of atmyc2 spa1 double mutants suggest that whereas MYC2 and SPA1 act redundantly to suppress photomorphogenic growth in the dark, they function synergistically for the suppression of photomorphogenic growth in the light. Our studies have also revealed that MYC2-mediated ABA and JA responses are further modulated by SPA1. Taken together, this study demonstrates the molecular and physiological interrelations of MYC2 and SPA1 in light, ABA, and JA signaling pathways.

Gangappa, Sreeramaiah N.; Prasad, V. Babu Rajendra; Chattopadhyay, Sudip

2010-01-01

220

Dlx1&2 and Mash1 Transcription Factors Control MGE and CGE Patterning and Differentiation through Parallel and Overlapping Pathways  

PubMed Central

Here we define the expression of ?100 transcription factors (TFs) in progenitors and neurons of the developing mouse medial and caudal ganglionic eminences, anlage of the basal ganglia and pallial interneurons. We have begun to elucidate the transcriptional hierarchy of these genes with respect to the Dlx homeodomain genes, which are essential for differentiation of most ?-aminobutyric acidergic projection neurons of the basal ganglia. This analysis identified Dlx-dependent and Dlx-independent pathways. The Dlx-independent pathway depends in part on the function of the Mash1 basic helix-loop-helix (b-HLH) TF. These analyses define core transcriptional components that differentially specify the identity and differentiation of the globus pallidus, basal telencephalon, and pallial interneurons.

Long, Jason E.; Cobos, Inma; Potter, Greg B.

2009-01-01

221

Three redundant brassinosteroid early response genes encode putative bHLH transcription factors required for normal growth.  

PubMed Central

Brassinosteroids (BRs) are a class of polyhydroxylated steroids that are important regulators of plant growth and development. We have identified three closely related basic helix-loop-helix (bHLH) transcription factors, BEE1, BEE2, and BEE3, as products of early response genes required for full BR response. Comparison of the phenotypes of plants that overexpress BEE1 with bee1 bee2 bee3 triple-knockout mutant plants suggests that BEE1, BEE2, and BEE3 are functionally redundant positive regulators of BR signaling. Expression of BEE1, BEE2, and BEE3 is also regulated by other hormones, notably abscisic acid (ABA), a known antagonist of BR signaling. Reduced ABA response in plants overexpressing BEE1 suggests that BEE proteins may function as signaling intermediates in multiple pathways.

Friedrichsen, Danielle M; Nemhauser, Jennifer; Muramitsu, Takamichi; Maloof, Julin N; Alonso, Jose; Ecker, Joseph R; Furuya, Masaki; Chory, Joanne

2002-01-01

222

bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells.  

PubMed

Multipotent neural progenitor cells (NPCs) undergo self-renewal while producing neurons, astrocytes, and oligodendrocytes. These processes are controlled by multiple basic helix-loop-helix (bHLH) fate determination factors, which exhibit different functions by posttranslational modifications. Furthermore, depending on the expression dynamics, each bHLH factor seems to have two contradictory functions, promoting NPC proliferation and cell-cycle exit for differentiation. The oscillatory expression of multiple bHLH factors correlates with the multipotent and proliferative state, whereas sustained expression of a selected single bHLH factor regulates the fate determination. bHLH factors also regulate direct reprogramming of adult somatic cells into neurons and oligodendrocytes. Thus, bHLH factors play key roles in development and regeneration of the nervous system. Here, we review versatile functions of bHLH factors, focusing on telencephalic development. PMID:24698265

Imayoshi, Itaru; Kageyama, Ryoichiro

2014-04-01

223

The emerging role of Twist proteins in hematopoietic cells and hematological malignancies  

PubMed Central

Twist1 and Twist2 (Twist1–2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1–2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1–2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies.

Merindol, N; Riquet, A; Szablewski, V; Eliaou, J-F; Puisieux, A; Bonnefoy, N

2014-01-01

224

HEB and E2A function as SMAD/FOXH1 cofactors  

PubMed Central

Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix–loop–helix (bHLH) proteins—HEB and E2A—bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.

Yoon, Se-Jin; Wills, Andrea E.; Chuong, Edward; Gupta, Rakhi; Baker, Julie C.

2011-01-01

225

BHLHB3: a candidate tumor suppressor in lung cancer.  

PubMed

BHLHB3 is a basic helix-loop-helix (bHLH) domain-containing protein that acts as a transcriptional repressor. We found that BHLHB3 transcript levels were low in three human lung cancer cell lines and downregulated in human lung adenocarcinomas as compared to normal lung tissue. BHLHB3 gene overexpression inhibited colony formation of A549, NCI-H520 and NCI-H596 lung cancer cells. The reduced colony growth was likely due to inhibition of cell proliferation as suggested by the downregulation of cyclin D1 (CCND1) expression in NCI-H520 cells transfected to overexpress the BHLHB3 gene; no evidence of apoptosis was observed. These results point to the potential role of the BHLHB3 protein as a tumor suppressor for lung cancer. PMID:18223678

Falvella, F S; Colombo, F; Spinola, M; Campiglio, M; Pastorino, U; Dragani, T A

2008-06-12

226

Homeodomain-Leucine Zipper II family of transcription factors to the limelight: central regulators of plant development.  

PubMed

The Arabidopsis genome encodes 10 Homeodomain-Leucine Zipper (HD-Zip) II transcription factors that can be subdivided into 4 clades (?-?). All the ? (ARABIDOPSIS THALIANA HOMEOBOX 2 [ATHB2], HOMEOBOX ARABIDOPSIS THALIANA 1 [HAT1], HAT2) and ? (HAT3, ATHB4) genes are regulated by light quality changes (Low Red [R]/Far-Red [FR]) that induce the shade avoidance response in most of the angiosperms. HD-Zip II? and HD-Zip II? transcription factors function as positive regulators of shade avoidance, and there is evidence that at least ATHB2 is directly positively regulated by the basic Helix-Loop-Helix (bHLH) proteins PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5. Recent evidence demonstrate that, in addition to their function in shade avoidance, HD-Zip II? and HD-Zip II? proteins play an essential role in plant development from embryogenesis onwards in a white light environment. PMID:23838958

Carabelli, Monica; Turchi, Luana; Ruzza, Valentino; Morelli, Giorgio; Ruberti, Ida

2013-09-01

227

A mutually assured destruction mechanism attenuates light signaling in Arabidopsis.  

PubMed

After light-induced nuclear translocation, phytochrome photoreceptors interact with and induce rapid phosphorylation and degradation of basic helix-loop-helix transcription factors, such as PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), to regulate gene expression. Concomitantly, this interaction triggers feedback reduction of phytochrome B (phyB) levels. Light-induced phosphorylation of PIF3 is necessary for the degradation of both proteins. We report that this PIF3 phosphorylation induces, and is necessary for, recruitment of LRB [Light-Response Bric-a-Brack/Tramtrack/Broad (BTB)] E3 ubiquitin ligases to the PIF3-phyB complex. The recruited LRBs promote concurrent polyubiqutination and degradation of both PIF3 and phyB in vivo. These data reveal a linked signal-transmission and attenuation mechanism involving mutually assured destruction of the receptor and its immediate signaling partner. PMID:24904166

Ni, Weimin; Xu, Shou-Ling; Tepperman, James M; Stanley, David J; Maltby, Dave A; Gross, John D; Burlingame, Alma L; Wang, Zhi-Yong; Quail, Peter H

2014-06-01

228

Homeodomain-Leucine zipper II family of transcription factors to the limelight  

PubMed Central

The Arabidopsis genome encodes 10 Homeodomain-Leucine Zipper (HD-Zip) II transcription factors that can be subdivided into 4 clades (?–?). All the ? (ARABIDOPSIS THALIANA HOMEOBOX 2 [ATHB2], HOMEOBOX ARABIDOPSIS THALIANA 1 [HAT1], HAT2) and ? (HAT3, ATHB4) genes are regulated by light quality changes (Low Red [R]/Far-Red [FR]) that induce the shade avoidance response in most of the angiosperms. HD-Zip II? and HD-Zip II? transcription factors function as positive regulators of shade avoidance, and there is evidence that at least ATHB2 is directly positively regulated by the basic Helix-Loop-Helix (bHLH) proteins PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5. Recent evidence demonstrate that, in addition to their function in shade avoidance, HD-Zip II? and HD-Zip II? proteins play an essential role in plant development from embryogenesis onwards in a white light environment.

Carabelli, Monica; Turchi, Luana; Ruzza, Valentino; Morelli, Giorgio; Ruberti, Ida

2013-01-01

229

Assignment of the hypoxia-inducible factor 1{alpha} gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q  

SciTech Connect

Hypoxia-inducible factor 1 (HIF-1) is a basic helix-loop-helix transcription factor that mediates homeostatic responses to hypoxia. HIF-1 is a heterodimer consisting of HIF-1{alpha} which is encoded by the HIF1A gene, complexes with HIF-1{beta}, which is encoded by the ARNT gene. In this paper we report the assignment of Hif1a and HIF1A to mouse chromosome 12 and human chromosome 14, respectively. HIF1A was assigned to human chromosome 14q21-q24 by analysis of somatic cell hybrids and by fluorescence in situ hybridization. Hif1a was localized by interspecific backcross analysis within a region of mouse chromosome 12 encompassing >30 cM that demonstrates conservation of synteny with a region of human chromosome 14 extending from PAX9 at 14q12-q13 to IGHC at 14q32.33. 12 refs., 2 figs.

Semenza, G.L.; Rue, E.A.; Iyer, N.V. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others] [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); and others

1996-06-15

230

The Notch Effector Hey1 Associates with Myogenic Target Genes to Repress Myogenesis*  

PubMed Central

Members of the Hey family of transcriptional repressors are basic helix-loop-helix proteins that are thought to act downstream of Notch in diverse tissues. Although forced expression of Hey1, a target of Notch in myoblasts, is sufficient to recapitulate inhibitory effects of the pathway on differentiation, how Hey1 interferes with myogenic transcription has not been fully elucidated. We provide multiple lines of evidence that Hey1 does not target the intrinsic transcriptional activity of the skeletal muscle master regulator MyoD. Our results indicate instead that Hey1 is recruited to the promoter regions of myogenin and Mef2C, two genes whose induction is critical for myogenesis. Expression of Hey1 in C2C12 myoblasts correlates with reduced recruitment of MyoD to these promoters, arguing that Hey1 inhibits myogenesis by associating with and repressing expression of key myogenic targets.

Buas, Matthew F.; Kabak, Shara; Kadesch, Tom

2010-01-01

231

Regulation of HDAC9 Gene Expression by MEF2 Establishes a Negative-Feedback Loop in the Transcriptional Circuitry of Muscle Differentiation?  

PubMed Central

Skeletal muscle development is controlled by the myocyte enhancer factor (MEF2) and myogenic basic helix-loop-helix (bHLH) families of transcription factors, which associate and synergistically activate muscle gene expression. Muscle differentiation is further reinforced by positive-feedback loops in which myogenic bHLH proteins activate their own expression and the expression of MEF2, while MEF2 stimulates expression of myogenic bHLH genes and the Mef2c gene. Here we describe a myogenic negative-feedback loop that consists of MEF2 proteins and the transcriptional repressor histone deacetylase 9 (HDAC9). We show that the HDAC9 gene is a direct transcriptional target of MEF2 in vitro and in vivo. HDAC9 can associate with MEF2 proteins and suppress their transcriptional activity. The transcriptional repressor HDAC9 thus forms a negative-feedback loop in the transcriptional circuitry of muscle differentiation.

Haberland, Michael; Arnold, Michael A.; McAnally, John; Phan, Dillon; Kim, Yuri; Olson, Eric N.

2007-01-01

232

Evolutionary aspects of variability in bHLH orthologous families: insights from the pearl oyster, Pinctada fucata.  

PubMed

Basic helix-loop-helix (bHLH) transcription factors play significant roles in multiple biological processes in metazoan cells. In recent work, we showed that three orthologous HLH families, pearl, amber, and peridot, have apparently been lost in the Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens lineages. To further address the gain and loss of bHLH proteins during bilaterian evolution, we examined the genome of the pearl oyster, Pinctada fucata, which has recently been sequenced. We characterized the putative full set 65 bHLH genes and showed that genes previously categorized into the orthologous family PTFb, actually fall into two distinct orthologous families, 48-related-1 and 48-related-2. We also identified a novel orthologous family, clockwork orange. Based on these newly identified orthologous family members and on orphan bHLH factors, we propose that genes encoding bHLH factors in bilaterians are not as evolutionarily stable as previously thought. PMID:24125650

Gyoja, Fuki; Satoh, Nori

2013-10-01

233

Cellular patterns of transcription factor expression in developing cortical interneurons.  

PubMed

Most gamma-aminobutyric acidergic interneurons in the neocortex and hippocampus are derived from subpallial progenitors in the medial ganglionic eminence and migrate tangentially to the pallium, where they differentiate into a diverse set of neuronal subtypes. Toward elucidating the mechanisms underlying the generation of interneuron diversity, we have studied in mice the expression patterns in differentiating and mature neocortical interneurons of 8 transcription factors, including 6 homeobox (Dlx1, Dlx2, Dlx5, Arx, Lhx6, Cux2), 1 basic helix-loop-helix, (NPAS1), and 1 bZIP (MafB). Their patterns of expression change during interneuron differentiation and show distinct distributions within interneuron subpopulations in adult neocortex. This study is a first step to define the combinatorial codes of transcription factors that participate in regulating the specification and function of cortical interneuron subtypes. PMID:16766712

Cobos, Inma; Long, Jason E; Thwin, Myo T; Rubenstein, John L

2006-07-01

234

Modified bimolecular fluorescence complementation assay to study the inhibition of transcription complex formation by JAZ proteins.  

PubMed

The jasmonate (JA) ZIM-domain (JAZ) proteins of Arabidopsis thaliana repress JA signaling and negatively regulate the JA responses. Recently, JAZ proteins have been found to inhibit the transcriptional function of several transcription factors, among which the basic helix-loop-helix (bHLH) (GLABRA3 [GL3], ENHANCER OF GLABRA3 [EGL3], and TRANSPARENT TESTA8 [TT8]) and R2R3-MYB (GL1 and MYB75) that can interact with each other to form bHLH-MYB complexes and further control gene expression. The bimolecular fluorescence complementation (BiFC) assay is a widely used technique to study protein-protein interactions in living cells. Here we describe a modified BiFC experimental procedure to study the inhibition of the formation of the bHLH (GL3)-MYB (GL1) complex by JAZ proteins. PMID:23615997

Qi, Tiancong; Song, Susheng; Xie, Daoxin

2013-01-01

235

Network Theory Inspired Analysis of Time-Resolved Expression Data Reveals Key Players Guiding P. patens Stem Cell Development  

PubMed Central

Transcription factors (TFs) often trigger developmental decisions, yet, their transcripts are often only moderately regulated and thus not easily detected by conventional statistics on expression data. Here we present a method that allows to determine such genes based on trajectory analysis of time-resolved transcriptome data. As a proof of principle, we have analysed apical stem cells of filamentous moss (P. patens) protonemata that develop from leaflets upon their detachment from the plant. By our novel correlation analysis of the post detachment transcriptome kinetics we predict five out of 1,058 TFs to be involved in the signaling leading to the establishment of pluripotency. Among the predicted regulators is the basic helix loop helix TF PpRSL1, which we show to be involved in the establishment of apical stem cells in P. patens. Our methodology is expected to aid analysis of key players of developmental decisions in complex plant and animal systems.

Busch, Hauke; Boerries, Melanie; Rensing, Stefan A.

2013-01-01

236

Proprioceptor pathway development is dependent on Math1  

NASA Technical Reports Server (NTRS)

The proprioceptive system provides continuous positional information on the limbs and body to the thalamus, cortex, pontine nucleus, and cerebellum. We showed previously that the basic helix-loop-helix transcription factor Math1 is essential for the development of certain components of the proprioceptive pathway, including inner-ear hair cells, cerebellar granule neurons, and the pontine nuclei. Here, we demonstrate that Math1 null embryos lack the D1 interneurons and that these interneurons give rise to a subset of proprioceptor interneurons and the spinocerebellar and cuneocerebellar tracts. We also identify three downstream genes of Math1 (Lh2A, Lh2B, and Barhl1) and establish that Math1 governs the development of multiple components of the proprioceptive pathway.

Bermingham, N. A.; Hassan, B. A.; Wang, V. Y.; Fernandez, M.; Banfi, S.; Bellen, H. J.; Fritzsch, B.; Zoghbi, H. Y.

2001-01-01

237

NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development  

PubMed Central

SUMMARY A key factor in the genetically programmed development of the nervous system is the death of massive numbers of neurons. Therefore, genetic mechanisms governing cell survival are of fundamental importance to developmental neuroscience. We report that inner ear sensory neurons are dependent on a basic helix-loop-helix transcription factor called NeuroD for survival during differentiation. Mice lacking NeuroD protein exhibit no auditory evoked potentials, reflecting a profound deafness. DiI fiber staining, immunostaining and cell death assays reveal that the deafness is due to the failure of inner ear sensory neuron survival during development. The affected inner ear sensory neurons fail to express neurotrophin receptors, TrkB and TrkC, suggesting that the ability of NeuroD to support neuronal survival may be directly mediated through regulation of responsiveness to the neurotrophins.

Kim, Woo-Young; Fritzsch, Bernd; Serls, Amanda; Bakel, Leigh Anne; Huang, Eric J.; Reichardt, Louis F.; Barth, Daniel S.; Lee, Jacqueline E.

2009-01-01

238

Accurate discrimination of bHLH domains in plants, animals, and fungi using biologically meaningful sites  

PubMed Central

Background The highly conserved bHLH (basic Helix-Loop-Helix) domain, found in many transcription factors, has been well characterized separately in Plants, Animals, and Fungi. While conserved, even functionally constrained sites have varied since the Eukarya split. Our research identifies those slightly variable sites that were highly characteristic of Plants, Animals, or Fungi. Results Through discriminant analysis, we identified five highly discerning DNA-binding amino acid sites. Additionally, by incorporating Kingdom specific HMMs, we were able to construct a tool to quickly and accurately identify and classify bHLH sequences using these sites. Conclusions We conclude that highly discerning sites identified through our analysis were likely under functional constraints specific to each Kingdom. We also demonstrated the utility of our tool by identifying and classifying previously unknown bHLH domains in both characterized genomes and from sequences in a large environmental sample.

2012-01-01

239

Binding of carbon nanotube to BMP receptor 2 enhances cell differentiation and inhibits apoptosis via regulating bHLH transcription factors.  

PubMed

Biomaterials that can drive stem cells to an appropriate differentiation level and decrease apoptosis of transplanted cells are needed in regenerative medicine. Nanomaterials are promising novel materials for such applications. Here we reported that carboxylated multiwalled carbon nanotube (MWCNT 1) promotes myogenic differentiation of mouse myoblast cells and inhibits cell apoptosis under the differentiation conditions by regulating basic helix-loop-helix transcription factors. MWCNT 1 attenuates bone morphogenetic protein receptor (BMPR) signaling activity by binding to BMPR2 and attenuating the phosphorylation of BMPR1. This molecular understanding allowed us to tune stem cell differentiation to various levels by chemical modifications, demonstrating human control of biological activities of nanoparticles and opening an avenue for potential applications of nanomaterials in regenerative medicine. PMID:22573038

Zhang, Y; Mu, Q; Zhou, H; Vrijens, K; Roussel, M F; Jiang, G; Yan, B

2012-01-01

240

Nuclear localized protein-1 (Nulp1) increases cell death of human osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein  

SciTech Connect

Nuclear localized protein-1 (Nulp1) is a recently identified gene expressed in mouse and human tissues particularly during embryonic development. Nulp1 belongs to the family of basic helix-loop-helix (bHLH) proteins that are important in development. The precise function of Nulp1 in cells is however not known. We observed that overexpression of Nulp1 induces a large increase in cell death of human osteosarcoma Saos2 cells with DNA fragmentation. In mouse N2A neuroblastoma cells Nulp1 affected cell proliferation and sensitized cells towards death induced by staurosporine. Staining using a novel antibody localized Nulp1 mainly to the cell nucleus and to some extent to the cytoplasm. Nulp1 binds the X-linked inhibitor of apoptosis protein (XIAP) and this interaction was increased during cell death. These results indicate that Nulp1 plays a role in cell death control and may influence tumor growth.

Steen, Hakan [Department of Neuroscience, Uppsala University, Biomedical Centre, Box 587, Husargatan 3, SE-75123 Uppsala (Sweden); Lindholm, Dan [Department of Neuroscience, Uppsala University, Biomedical Centre, Box 587, Husargatan 3, SE-75123 Uppsala (Sweden); Minerva Institute for Medical Research, Biomedicum Helsinki, Helsinki (Finland)], E-mail: dan.lindholm@neuro.uu.se

2008-02-08

241

Id: A Target of BMP Signaling  

NSDL National Science Digital Library

Cytokines of the transforming growth factor-β (TGF-β) superfamily transduce their signals by activating receptor-regulated Smads (R-Smads). Distinct R-Smads or combinations of R-Smads are activated by TGF-β, activin, or bone morphogenetic proteins (BMPs). R-Smads activated by BMPs induce expression of Id proteins, which act as inhibitors of differentiation and stimulators of cell growth by inhibiting the function of basic helix-loop-helix transcription factors. In endothelial cells, TGF-β binds to two distinct type I receptor serine-threonine kinases, ALK-5 and ALK-1; the latter activates the same R-Smads that are activated by BMP and induces synthesis of Id (inhibitor of differentation or inhibitor of DNA binding) proteins. Growing evidence suggests that Id proteins may play crucial roles in angiogenesis, neurogenesis, and osteogenesis and act as key molecules in regulating biological responses induced by BMPs and TGF-β.

Kohei Miyazono (University of Tokyo;Department of Molecular Pathology, Graduate School of Medicine REV); Keiji Miyazawa (University of Tokyo;Department of Molecular Pathology, Graduate School of Medicine REV)

2002-09-24

242

The emerging roles of TCF4 in disease and development.  

PubMed

Genome-wide association studies have identified common variants in transcription factor 4 (TCF4) as susceptibility loci for schizophrenia, Fuchs' endothelial corneal dystrophy, and primary sclerosing cholangitis. By contrast, rare TCF4 mutations cause Pitt-Hopkins syndrome, a disorder characterized by intellectual disability and developmental delay, and have also been described in patients with other neurodevelopmental disorders. TCF4 therefore sits at the nexus between common and rare disorders. TCF4 interacts with other basic helix-loop-helix proteins, forming transcriptional networks that regulate the differentiation of several distinct cell types. Here, we review the role of TCF4 in these seemingly diverse disorders and discuss recent data implicating TCF4 as an important regulator of neurodevelopment and epithelial-mesenchymal transition. PMID:24594265

Forrest, Marc P; Hill, Matthew J; Quantock, Andrew J; Martin-Rendon, Enca; Blake, Derek J

2014-06-01

243

Functional Identification of the Mouse Circadian Clock Gene by Transgenic BAC Rescue  

PubMed Central

Summary As a complementary approach to positional cloning, we used in vivo complementation with bacterial artificial chromosome (BAC) clones expressed in transgenic mice to identify the circadian Clock gene. A 140 kb BAC transgene completely rescued both the long period and the loss-of-rhythm phenotypes in Clock mutant mice. Analysis with overlapping BAC transgenes demonstrates that a large transcription unit spanning “100,000 base pairs is the Clock gene and encodes a novel basic–helix-loop-helix–PAS domain protein. Overexpression of the Clock transgene can shorten period length beyond the wild-type range, which provides additional evidence that Clock is an integral component of the circadian pacemaking system. Taken together, these results provide a proof of principle that “cloning by rescue” is an efficient and definitive method in mice.

Antoch, Marina P.; Song, Eun-Joo; Chang, Anne-Marie; Vitaterna, Martha Hotz; Zhao, Yaliang; Wilsbacher, Lisa D.; Sangoram, Ashvin M.; King, David P.; Pinto, Lawrence H.; Takahashi, Joseph S.

2013-01-01

244

Casein kinase II increases the transcriptional activities of MRF4 and MyoD independently of their direct phosphorylation.  

PubMed Central

The myogenic regulatory factors (MRFs) are a subclass of a much larger group of basic helix-loop-helix transcription factors which includes members of the E protein such as E47, E2-2, and HEB. Although the MRFs are unique in their ability to confer a myogenic phenotype on nonmuscle cells, they require E protein partners to form a MRF-E protein heterodimer, which represents the functional myogenesis-inducing complex. The mechanisms controlling homodimer and heterodimer formation in vivo remain largely unknown, although it is likely that posttranslational modification of one or both basic helix-loop-helix partners is critical to this regulatory event. In this respect, MyoD and MRF4, both members of the MRF family, exist in vivo as phosphoproteins and contains multiple consensus phosphorylation sites, including sites for casein kinase II (CKII) phosphorylation. In this study, we demonstrate that overexpression of CKII increases the transcriptional activities of MRF4 and MyoD in vivo. Interestingly, mutation of the individual CKII sites within MRF4 and MyoF does not alter the ability of CKII to enhance MRF transcriptional activity, suggesting that the effect of CKII expression on the MRFs is indirect. Given that the MRFs require dimerization with E protein partners to activate muscle-specific transcription, the effects of CKII expression on E protein function also were examined. Our studies show that E47 serves as an in vitro substrate for CKII and that CKII-phosphorylated E-47 proteins no longer bind to DNA. These observations were confirmed by in vivo experiments showing that overexpressing of CKII produces a dramatic reduction in E47 homodimer-directed transcription. We conclude from these studies that CKII may act as a positive regulator of myogenesis by preventing E protein homodimers from binding to muscle gene regulatory elements.

Johnson, S E; Wang, X; Hardy, S; Taparowsky, E J; Konieczny, S F

1996-01-01

245

Id1 Expression Promotes T Regulatory Cell Differentiation by Facilitating TCR Costimulation.  

PubMed

T regulatory (Treg) cells play crucial roles in the regulation of cellular immunity. The development of Treg cells depends on signals from TCRs and IL-2Rs and is influenced by a variety of transcription factors. The basic helix-loop-helix proteins are known to influence TCR signaling thresholds. Whether this property impacts Treg differentiation is not understood. In this study, we interrogated the role of basic helix-loop-helix proteins in the production of Treg cells using the CD4 promoter-driven Id1 transgene. We found that Treg cells continued to accumulate as Id1 transgenic mice aged, resulting in a significant increase in Treg cell counts in the thymus as well as in the periphery compared with wild-type controls. Data from mixed bone marrow assays suggest that Id1 acts intrinsically on developing Treg cells. We made a connection between Id1 expression and CD28 costimulatory signaling because Id1 transgene expression facilitated the formation of Treg precursors in CD28(-/-) mice and the in vitro differentiation of Treg cells on thymic dendritic cells despite the blockade of costimulation by anti-CD80/CD86. Id1 expression also allowed in vitro Treg differentiation without anti-CD28 costimulation, which was at least in part due to enhanced production of IL-2. Notably, with full strength of costimulatory signals, however, Id1 expression caused modest but significant suppression of Treg induction. Finally, we demonstrate that Id1 transgenic mice were less susceptible to the induction of experimental autoimmune encephalomyelitis, thus illustrating the impact of Id1-mediated augmentation of Treg cell levels on cellular immunity. PMID:24920844

Liu, Chen; Wang, Hong-Cheng; Yu, Sen; Jin, Rong; Tang, Hui; Liu, Yuan-Feng; Ge, Qing; Sun, Xiao-Hong; Zhang, Yu

2014-07-15

246

Differentiated embryo-chondrocyte expressed gene 1 regulates p53-dependent cell survival versus cell death through macrophage inhibitory cytokine-1  

PubMed Central

Activation of p53 upon DNA damage induces an array of target genes, leading to cell cycle arrest and/or apoptosis. However, the mechanism by which the cell fate is controlled by p53 remains to be clarified. Previously, we showed that DEC1, a basic helix–loop–helix transcription factor and a target of p53, is capable of inducing cell cycle arrest and mediating DNA damage-induced premature senescence. Here, we found that ectopic expression of DEC1 inhibits, whereas knockdown of DEC1 enhances, DNA damage-induced cell death. Surprisingly, we showed that the anti–cell-death activity of DEC1 is p53 dependent, but DEC1 does not directly modulate p53 expression. Instead, we showed that DEC1 inhibits the ability of p53 to induce macrophage inhibitory cytokine-1 (MIC-1), but not other prosurvival/proapoptotic targets, including p21 and Puma. Importantly, we showed that upon binding to their respective response elements on the MIC-1 promoter, DEC1 and p53 physically interact on the MIC-1 promoter via the basic helix–loop–helix domain in DEC1 and the tetramerization domain in p53, which likely weakens the DNA-binding activity of p53 to the MIC-1 promoter. Finally, we found that depletion of MIC-1 abrogates the ability of DEC1 to attenuate DNA damage-induced cell death. Together, we hypothesize that DEC1 controls the response of p53-dependent cell survival vs. cell death to a stress signal through MIC-1.

Qian, Yingjuan; Jung, Yong-Sam; Chen, Xinbin

2012-01-01

247

Citrus tristeza virus p23: a unique protein mediating key virus-host interactions  

PubMed Central

The large RNA genome of Citrus tristeza virus (CTV; ca. 20 kb) contains 12 open reading frames, with the 3?-terminal one corresponding to a protein of 209 amino acids (p23) that is expressed from an abundant subgenomic RNA. p23, an RNA-binding protein with a putative zinc-finger domain and some basic motifs, is unique to CTV because no homologs have been found in other closteroviruses, including the type species of the genus Beet yellows virus (despite both viruses having many homologous genes). Consequently, p23 might have evolved for the specific interaction of CTV with its citrus hosts. From a functional perspective p23 has been involved in many roles: (i) regulation of the asymmetrical accumulation of CTV RNA strands, (ii) induction of the seedling yellows syndrome in sour orange and grapefruit, (iii) intracellular suppression of RNA silencing, (iv) elicitation of CTV-like symptoms when expressed ectopically as a transgene in several Citrus spp., and (v) enhancement of systemic infection (and virus accumulation) in sour orange and CTV release from the phloem in p23-expressing transgenic sweet and sour orange. Moreover, transformation of Mexican lime with intron-hairpin constructs designed for the co-inactivation of p23 and the two other CTV silencing suppressors results in complete resistance against the homologous virus. From a cellular point of view, recent data indicate that p23 accumulates preferentially in the nucleolus, being the first closterovirus protein with such a subcellular localization, as well as in plasmodesmata. These major accumulation sites most likely determine some of the functional roles of p23.

Flores, Ricardo; Ruiz-Ruiz, Susana; Soler, Nuria; Sanchez-Navarro, Jesus; Fagoaga, Carmen; Lopez, Carmelo; Navarro, Luis; Moreno, Pedro; Pena, Leandro

2013-01-01

248

Bursitis (Beyond the Basics)  

MedlinePLUS

... information: Arthritis (Beyond the Basics) Patient information: Elbow tendinopathy (tennis and golf elbow) (Beyond the Basics) Patient ... is a typical complaint. (See "Patient information: Elbow tendinopathy (tennis and golf elbow) (Beyond the Basics)" .) Treatment ...

249

Blue light photoreceptors are required for the stability and function of a resistance protein mediating viral defense in Arabidopsis  

PubMed Central

This light-perceiving ability of plants requires the activities of proteins termed photoreceptors. In addition to various growth and developmental processes, light also plays a role in plant defense against pathogens and is required for activation of several defense genes and regulation of the cell death response. However, the molecular or biochemical basis of light modulated regulation of defense signaling is largely unclear. We demonstrate a direct role for blue-light photoreceptors in resistance (R) protein-mediated plant defense against Turnip Crinkle Virus (TCV) in Arabidopsis. The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are specifically required for maintaining the stability of the R protein HRT, and thereby resistance to TCV. Exogenous application of the phytohormone salicylic acid elevates HRT levels in phot2 but not in cry2 background. These data indicate that CRY2 and PHOT2 function distinctly in maintaining post-transcriptional stability of HRT. HRT-mediated resistance is also dependent on CRY1 and PHOT1 proteins, but these do not contribute to the stability of HRT. HRT interacts with the CRY2/PHOT2-interacting protein COP1, a E3 ubiquitin ligase. Exogenous application of a proteasome inhibitor prevents blue-light-dependent degradation of HRT, suggesting that HRT is degraded via the 26S proteasome. These and the fact that PHOT2 interacts directly with the R protein RPS2 suggest that blue-light photoreceptors might be involved in regulation and/or signaling mediated by several R proteins.

Jeong, Rae-Dong; Kachroo, Aardr

2010-01-01

250

Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosome relocalization, and spindle pole body morphogenesis  

PubMed Central

We identify a large coiled-coil protein, Sme4/PaMe4, that is highly conserved among the large group of Sordariales and plays central roles in two temporally and functionally distinct aspects of the fungal sexual cycle: first as a component of the meiotic synaptonemal complex (SC) and then, after disappearing and reappearing, as a component of the spindle pole body (SPB). In both cases, the protein mediates spatial juxtaposition of two major structures: linkage of homolog axes through the SC and a change in the SPB from a planar to a bent conformation. Corresponding mutants exhibit defects, respectively, in SC and SPB morphogenesis, with downstream consequences for recombination and astral-microtubule nucleation plus postmeiotic nuclear migration. Sme4 is also required for reorganization of recombination complexes in which Rad51, Mer3, and Msh4 foci relocalize from an on-axis position to a between-axis (on-SC) position concomitant with SC installation. Because involved recombinosome foci represent total recombinational interactions, these dynamics are irrespective of their designation for maturation into cross-overs or noncross-overs. The defined dual roles for Sme4 in two different structures that function at distinct phases of the sexual cycle also provide more functional links and evolutionary dynamics among the nuclear envelope, SPB, and SC.

Espagne, Eric; Vasnier, Christelle; Storlazzi, Aurora; Kleckner, Nancy E.; Silar, Philippe; Zickler, Denise; Malagnac, Fabienne

2011-01-01

251

Regulation of Replication Termination in Schizosaccharomyces pombe by Reb1 Protein-Mediated Action at a Distance  

PubMed Central

The mechanisms of DNA transactions driven by long range protein-mediated inter and intra-chromosomal interactions are currently of considerable general interest. Here, we report that site-specific replication termination catalyzed by the dimeric Reb1 protein of Schizosaccharomyces. pombe at its cognate replication termini (Ter) did not occur independently at each site but was modulated by the Reb1-mediated interactions between pairs of Ter sites located either in the same or in different chromosomes. The interactions between two Ter sites in cis, placed in a mutually anti-parallel orientation, caused looping out of the intervening DNA in vitro and enhancement of fork arrest in vivo. A Ter on chromosome 2 interacted pair-wise with two Ter sites located on chromosome1 by chromosome kissing. Mutational inactivation of the major interacting Ter on chromosome1 abolished or significantly reduced fork arrest at the Ter site on chromosome 2, thereby revealing a novel mechanism of control of replication termination.

Singh, Samarendra K.; Sabatinos, Sarah; Forsburg, Susan; Bastia, Deepak

2010-01-01

252

Adult Basic Education Basic Computer Literacy Handbook.  

ERIC Educational Resources Information Center

This handbook, in both English and Spanish versions, is intended for use with adult basic education (ABE) students. It contains five sections of basic computer literacy activities and information about the ABE computer literacy course offered at Dona Ana Community College (DACC) in New Mexico. The handbook begins with forewords by the handbook's…

Manini, Catalina M.; Cervantes, Juan

253

Basicity and optical basicities of slags  

NASA Astrophysics Data System (ADS)

Various terms used to define basicity are outlined. The concept of optical basicity is discussed and its relationships with the following are discussed: elemental partition between slag and metal phases for example S, P, and O; solubility of oxides in the slag phase; thermodynamic properties; and structure and certain physical properties of the slag.

Mills, K. C.

1992-02-01

254

BASIC Tools: Structured Programming Techniques in BASIC.  

ERIC Educational Resources Information Center

Structured programing is an attempt to formalize the logic and structure of computer programs. Examples of structured programing techniques in BASIC are provided. Two major disadvantages of this style of programing for the personal user are noted. (JN)

Moyer, Patrick C.

1985-01-01

255

CSF myelin basic protein  

MedlinePLUS

CSF myelin basic protein is a test to measure the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF). The CSF ... less than 4 ng/mL of myelin basic protein in the CSF. Note: ng/mL = nanogram per ...

256

Basic Cake Decorating Workbook.  

ERIC Educational Resources Information Center

Included in this student workbook for basic cake decorating are the following: (1) Drawings of steps in a basic way to ice a layer cake, how to make a paper cone, various sizes of flower nails, various sizes and types of tin pastry tubes, and special rose tubes; (2) recipes for basic decorating icings (buttercream, rose paste, and royal icing);…

Bogdany, Mel

257

Basic Construction Course Syllabus  

NSDL National Science Digital Library

This course syllabus provides an outline of a basic construction course. Students in this course learned "basic residential construction techniques with an emphasis on framing." The syllabus includes a basic course description and information on some class projects. This document may be downloaded in PDF file format.

Dickover, Jon

2011-12-07

258

Fiber Optics Basics  

NSDL National Science Digital Library

This pdf from OP-TEC, the National Center for Optics and Photonics Education, addresses basic concepts underlying the operation of fiber lasers. This free 26 page document supplements the fiber laser material presented in an Elements of Photonics Course by provided a more current and detailed description of how lasers operate. This course covers basic laser operations, basic structure of fiber lasers, pulsing methods, output characteristics of fiber lasers, and advanced structures.

2012-12-04

259

Basic Science Training Program.  

ERIC Educational Resources Information Center

These six learning modules were developed for Lake Michigan College's Basic Science Training Program, a workshop to develop good study skills while reviewing basic science. The first module, which was designed to provide students with the necessary skills to study efficiently, covers the following topics: time management; an overview of a study…

Brummel, Clete

260

Basic Electronics I.  

ERIC Educational Resources Information Center

Designed for use in basic electronics programs, this curriculum guide is comprised of twenty-nine units of instruction in five major content areas: Orientation, Basic Principles of Electricity/Electronics, Fundamentals of Direct Current, Fundamentals of Alternating Current, and Applying for a Job. Each instructional unit includes some or all of…

Robertson, L. Paul

261

Fluency with Basic Addition  

ERIC Educational Resources Information Center

Traditionally, learning basic facts has focused on rote memorization of isolated facts, typically through the use of flash cards, repeated drilling, and timed testing. However, as many experienced teachers have seen, "drill alone does not develop mastery of single-digit combinations." In contrast, a fluency approach to learning basic addition…

Garza-Kling, Gina

2011-01-01

262

Modular Basic Action Theories  

Microsoft Academic Search

In this paper we design a representation that allows writ- ing more compact and modular basic action theories, than it is currently possible. Moreover, such representation also provides formal foundations for reasoning about actions in OpenCyc by using Reiter's basic action theory formalism.

Yilan Gu; Mikhail Soutchanski

263

Understanding Basic Mechanics: Workbook  

NSDL National Science Digital Library

This workbook is designed to be used with the Understanding Basic Mechanics textbook in an introductory calculus-based physics course for science or engineering students. The text presents the basic subject matter, facilitating reference, while the workbook is used to ensure students have understood the reading, can interpret it appropriately, and can apply it to diverse situations.

Reif, Frederick

2006-07-22

264

Bambara Basic Course.  

ERIC Educational Resources Information Center

This text is a preliminary version of a basic course in the Bambara language. It is one of a series of short basic courses in African languages. Tutors' instructions appear in both English and French. Sixteen units make up the text; each consists of pattern drills in English and Bambara on a particular point of grammar. (CHK)

Stevick, Earl W.

265

Traumatic Brain Injury Basics  

MedlinePLUS

... Shopping cart Contact Us DVBIC Defense and Veterans Brain Injury Center Main menu Service Members & Veterans Family & Friends ... TBI Basics What is a TBI? A traumatic brain injury (TBI) can be classified as mild, moderate, severe ...

266

E-Mail Basics.  

ERIC Educational Resources Information Center

Offers electronic mail basics, mail etiquette and tips, interesting World Wide Web sites, and how to do a Web search. Includes Web sites that offer beginner tutorials and a glossary of Internet terms. (JOW)

Cohen, Sacha

1996-01-01

267

Brain Basics: Preventing Stroke  

MedlinePLUS

Brain Basics: Preventing Stroke Request free mailed brochure Table of Contents Introduction What is a Stroke? What ... Americans are protecting their most important asset—their brain. Are you? Stroke ranks as the fourth leading ...

268

Basic Electricity Materials  

NSDL National Science Digital Library

This site from SpaceTEC National Aerospace Technical Education Center presents basic materials electricity. Topics include safety, metric notations, atomic structure, instruments, electrical concepts, resistor and AC circuits, power supplies, circuit protection, relays, connections, and electrostatic states.

2010-11-24

269

BMP (Basic Metabolic Panel)  

MedlinePLUS

... Pages On This Site Apart from the Related Tests noted above, there are no other related pages on this site. Elsewhere On The Web MedlinePlus Medical Encyclopedia: Basic metabolic panel » See all ...

270

Wth Basic Art Materials  

ERIC Educational Resources Information Center

In this article, the author presents a checklist of basic materials for two-dimensional activities that are necessary for an elementary-school art program. She also provides a few tips on how to use them.

Herberholz, Barbara

2010-01-01

271

Basic Auditor Student Reference.  

National Technical Information Service (NTIS)

The reference was written to provide a consolidated reference source that encompasses the topics presented in the Basic Auditor Course Program of Instruction (POI). To accomplish this objective, it is structured in the same manner as the POI. Section numb...

1978-01-01

272

Basic Nuclear Science Information  

NSDL National Science Digital Library

This webpage from the Lawrence Berkeley National Laboratory contains an overview of the basic concepts in nuclear science. Nuclear structure, particle decay, nuclear reactions, and cosmic rays are briefly discussed. The page also contains helpful pictures to illustrate the concepts.

2009-10-30

273

Ed's Basic Histology Gallery  

NSDL National Science Digital Library

This website introduces the basic concepts of histology. The site is organized by different anatomical structures and provides a tutorial, histology slices and quiz for students for each structure presented.

2010-03-02

274

Radiation Protection Basics  

MedlinePLUS

... Basic Concepts of Radiation Protection time distance shielding Time The amount of radiation exposure increases and decreases ... exposure. How does EPA use the concept of time in radiation protection? When we set a radiation ...

275

Basics of Dusty Plasma  

SciTech Connect

The paper presents an introductory review of the basic physical processes in dusty plasmas. The topics to be addressed are dust charging, forces acting on dust grains, interaction between dust grains, and dust-plasma structures.

Ignatov, A.M. [Prokhorov Institute of General Physics, Russian Academy of Sciences, ul. Vavilova 38, Moscow, 119991 (Russian Federation)

2005-01-15

276

Understanding Basic Mechanics  

NSDL National Science Digital Library

This text is designed for an introductory calculus-based physics course for science or engineering students. Combined with its workbook, it forms a coherent introduction to basic mechanics. The text presents the basic subject matter, facilitating reference and review, while the workbook actively engages students in their learning to ensure that they have understood the reading, can interpret it appropriately, and can apply it to diverse situations.

Reif, Frederick

2006-07-22

277

Heterogeneous basic catalysis  

SciTech Connect

Heterogeneous acid catalysis attracted much attention primarily because heterogeneous acidic catalysts act as catalysts in petroleum refinery and are known as a main catalyst in the cracking process which is the largest process among the industrial chemical processes. In contrast to these extensive studies of heterogeneous acidic catalysts, fewer efforts have been given to the study of heterogeneous basic catalysts. The types of heterogeneous basic catalysts are listed in Table 1. Except for non-oxide catalysts, the basic sites are believed to be surface O atoms. The studies of heterogeneous catalysis have been continuous and progressed steadily. They have never been reviewed in the chemical Reviews before. It is more useful and informative to describe the studies of heterogeneous basic catalysis performed for a long period. In the present article, therefore, the cited papers are not restricted to those published recently, but include those published for the last 25 years. The paper first describes the generation of basic sites before describing methods used in the characterization of basic surfaces. These are indicator methods, temperature programmed desorption (TPD) of CO{sub 2}, UV absorption and luminescence spectroscopies, TPD of H{sub 2}, XPS, IR of CO{sub 2}, IR of pyrrole, and oxygen exchange between CO{sub 2} and the surface. The paper then discusses studies on the catalysis by heterogeneous basic catalysts. Some of these reactions are dehydration, dehydrogenation, hydrogenation, amination, alkylation, ring transformation, and reactions of organosilanes. Catalysts discussed are single component metal oxides, zeolites, non-oxide types, and superbasic catalysts. 141 refs.

Hattori, Hideshi [Hokkaido Univ., Sapporo (Japan). Center for Advanced Research of Energy Technology

1995-05-01

278

Excel 1 - The Basics  

NSDL National Science Digital Library

Spreadsheets are used to keep track of numbers and other data in an organized fashion. It is kind of like a big calculator. In this lesson you will learn the basics of Microsoft\\'s spreadsheet program, Excel. The tutorial link below will take you through the very basics of Excel. You will start with an Overview of what Excel is and what kinds of documents it is used to create. Watch the video from the link on the right hand side of the screen. ...

Brewer, Mrs.

2006-11-25

279

The New Basics.  

ERIC Educational Resources Information Center

To teach the New Basic Skills to all students, schools can adopt the five principles of high-performance firms: (1) develop clear goals; (2) provide opportunities to solve problems and the incentives to do so; (3) provide the training needed to pursue solutions effectively; (4) measure progress toward goals regularly; and (5) persevere and learn…

Murnane, Richard J.; Levy, Frank

1997-01-01

280

Focus on Basics, 1997.  

ERIC Educational Resources Information Center

Together, these four newsletters contain 36 articles devoted to adult literacy research and practice and the relationship between them. The following articles are included: "A Productive Partnership" (Richard J. Murnane, Bob Bickerton); "Welcome to 'Focus on Basics'" (Barbara Garner); "Applying Research on the Last Frontier" (Karen Backlund, Kathy…

Focus on Basics, 1997

1997-01-01

281

Computer Programming: BASIC.  

ERIC Educational Resources Information Center

This guide was prepared to help teachers of the Lincoln Public School's introductory computer programming course in BASIC to make the necessary adjustments for changes made in the course since the purchase of microcomputers and such peripheral devices as television monitors and disk drives, and the addition of graphics. Intended to teach a…

Fisher, Patience; And Others

282

Basic Soils. Revision.  

ERIC Educational Resources Information Center

This curriculum guide is designed for use in teaching a course in basic soils that is intended for college freshmen. Addressed in the individual lessons of the unit are the following topics: the way in which soil is formed, the physical properties of soil, the chemical properties of soil, the biotic properties of soil, plant-soil-water…

Montana State Univ., Bozeman. Dept. of Agricultural and Industrial Education.

283

Basic Media in Education.  

ERIC Educational Resources Information Center

Intended as a guide to the use of different media for use in the classroom, this document demonstrates alternative approaches that may be taken to depicting and communicating images and concepts to others. Some basic tools and materials--including a ruler, matte knife, rubber cement, stapler, felt-tip pens, paint brushes, and lettering pens--are…

Harrell, John

284

Burmese Basic Course.  

ERIC Educational Resources Information Center

These five volumes, comprising 65 lesson units, follow the Defense Language Institute audiolingual approach and general format. New materials, introduced in "basic dialogs," are followed by colloquial and literal translations, word lists, and in later lessons, by a variety of drills and reading exercises. A consonant chart and a transcribed list…

Defense Language Inst., Washington, DC.

285

GPS Receiver Basics  

NSDL National Science Digital Library

Students familiarize themselves â through trial and error â with the basics of GPS receiver operation. They view a receiver's satellite visibility screen as they walk in various directions and monitor their progress on the receiver's map. Students may enter waypoints and use the GPS information to guide them back to specific locations.

Integrated Teaching And Learning Program

286

ADULT BASIC EDUCATION.  

ERIC Educational Resources Information Center

THIS SEMINAR WAS CONCERNED WITH TECHNIQUES OF BASIC ADULT EDUCATION, BROAD POLICY, AND LEGISLATION. TOPICS OF ADDRESSES INCLUDED CANADIAN FACTS AND FIGURES, FRONTIER COLLEGE, ELLIOT LAKE CENTRE, LEASIDE EDUCATION ASSISTANCE PROJECT, INDIAN AFFAIRS, ADULT EDUCATION IN CALGARY, METROPOLITAN EDUCATIONAL TELEVISION ASSOCIATION, TECHNICAL AND…

CORNISH, D. JOHN

287

Basic Drafting: Book One.  

ERIC Educational Resources Information Center

The first of a two-book course in drafting, this manual consists of 13 topics in the following units: introduction to drafting, general safety, basic tools and lines, major equipment, applying for a job, media, lettering, reproduction, drawing sheet layout, architect's scale usage, civil engineer's scale usage, mechanical engineer's scale usage,…

Davis, Ronald; And Others

288

Analytical Electrochemistry: Basic Concepts  

NSDL National Science Digital Library

This module focuses on the basic concepts involved in dynamic electrochemistry when the net current is not zero - the combination of mass transfer and electrochemical reactions at the interface between solids and fluids. It is at an introductory level appropriate for undergraduates in their sophomore or junior years.

Kelly, Richard S.

2011-06-03

289

Perspectives on Plasmas: Basics  

NSDL National Science Digital Library

This website from Plasmas International presents the basic ideas of plasma physics. It includes a chart of temperature versus density that shows the many plasma states on Earth and in space, as well as ordinary matter. It includes a number of links to related sites.

2008-08-12

290

Basics of SCI Rehabilitation  

MedlinePLUS Videos and Cool Tools

... How Family Life Changes After SCI Empowering the Patient After SCI Pediatric Injuries Pediatric Spinal Cord Injury 101 The Basics of Pediatric SCI Rehabilitation Transitions for Children with SCI What are the main concerns of the patient after a spinal cord jury? What are the ...

291

Incentives in Basic Research  

Microsoft Academic Search

Individuals involved in basic research, like other workers, respond to incentives. Funding agencies provide implicit incentives when they specify the rules by which awards are made. The following analysis is an exercise in understanding incentives at an applied level. Specific rules are examined. What is the effect of rewarding past effort? What happens when a few large awards are replaced

Edward P. Lazear

1997-01-01

292

Incentives in Basic Research  

Microsoft Academic Search

Individuals involved in basic research, like other workers, respond to incentives. Funding agencies provide implicit incentives when they specify the rules by which awards are made. The following analysis is an exercise in understanding incentives at an applied level. Specific rules are examined and analyzed to determine their incentive effects. For example, what is the effect of rewarding past effort?

Edward P. Lazear

1996-01-01

293

Basic Research Symposium  

Microsoft Academic Search

The Basic Research Symposium is a special event with a five-year history at CHI. It is a hybrid between a mini-conference and a workshop that presents an opportunity for researchers from different disciplines to share their visions through exchanging new developments and insights from their own fields. The goal of the Symposium is to provide an interactive forum to promote

Susanne Jul; Leon Watts

1997-01-01

294

Basic Sciences - Pathogenetics  

Cancer.gov

The aim of the Pathogenetics Unit is to investigate genetic alterations underlying tumor development and progression. Emphasis is placed on the study of human cancer as it occurs in vivo, and on the integration of basic research, clinical information, and developing technologies.

295

Projectable Basic Electronics Kit.  

ERIC Educational Resources Information Center

Outlines advantages derived from constructing and using a Projectable Basic Electronics Kit and provides: (1) list of components; (2) diagrams of 10 finished components (resistor; capacitor; diode; switch; bulb; transistor; meter; variable capacitor; coil; connecting terminal); and (3) diode and transistor activities. (JN)

H'ng, John; And Others

1982-01-01

296

Basics of Plasma Physics  

Microsoft Academic Search

Basic properties of plasmas are introduced, which are valid for an extremely wide range of plasma parameters. Plasmas are\\u000a classified by different physical behaviour. The motion of charged particles in electromagnetic fields is revised with respect\\u000a to drift motions. Adiabatic invariants are discussed and the kinetic description of plasmas is briefly presented.

U. Schumacher

2005-01-01

297

Basic physics of insulators  

Microsoft Academic Search

A number of areas of basic insulator physics that have made considerable steps forward the last few years are reviewed, and it shown how these have affected the understanding of practical dielectrics and methods of data handling. The topics covered include mathematical techniques, advances in the computation of electric fields and the theory of dielectrics and space charges, novel experimental

H. J. Wintle

1990-01-01

298

Basics of Searching MEDLINE.  

National Technical Information Service (NTIS)

The Guide is designed to acquaint the health professional with the basic concepts and skills involved in using MEDLARS to retrieve information from its primary database, MEDLINE. It may be used in a formal training course or as a self-paced learning tool....

1989-01-01

299

Basic Internet Software Toolkit.  

ERIC Educational Resources Information Center

Once schools are connected to the Internet, the next step is getting network workstations configured for Internet access. This article describes a basic toolkit comprising software currently available on the Internet for free or modest cost. Lists URLs for Web browser, Telnet, FTP, file decompression, portable document format (PDF) reader,…

Buchanan, Larry

1998-01-01

300

Basic Terminal Forecast Strategies  

NSDL National Science Digital Library

This module is the first component of the Distance Learning Course 2, Producing Customer-Focused TAFs. Basic Terminal Forecast Strategies is comprised of two lessons that provide 1) an introduction to understanding aviation customers and their needs and 2) a technique to meet those needs by producing clear, concise, and consistent terminal aerodrome forecasts (TAFs).

Spangler, Tim

2006-09-22

301

Cloud Physics: The Basics  

NSDL National Science Digital Library

This website from the Oklahoma Weather Modification Program encourages students to initiate a debate on the controversy surrounding the issue of inducing or enhancing precipitation. The exercise describes the two basic tenets of cloud seeding: the Static Phase Hypothesis and the Dynamic Phase Hypothesis. Also provided are links to a weather and climate glossary and further information about clouds and precipitation.

Klatt, Michael L.

2008-01-14

302

Bell's Palsy (Beyond the Basics)  

MedlinePLUS

... Prognosis and treatment in adults Clinical manifestations of Lyme disease in adults Patient information: Bell's palsy (The Basics) Patient information: Lyme disease (The Basics) Patient information: Myasthenia gravis (The Basics) ...

303

Gene expression is dynamically regulated in retinal progenitor cells prior to and during overt cellular differentiation.  

PubMed

The retina is comprised of one glial and six neuronal populations that are generated from a multipotent pool of retinal progenitor cells (RPCs) during development. To give rise to these different cell types, RPCs undergo temporal identity transitions, displaying distinct gene expression profiles at different stages of differentiation. Little, however, is known about temporal differences in RPC identities prior to the onset of overt cellular differentiation, during the period when a retinal identity is gradually acquired. Here we examined the sequential onset of expression of regional markers (i.e., homeodomain transcription factors) and cell fate determinants (i.e., basic-helix-loop-helix transcription factors and neurogenic genes) in RPCs from the earliest appearance of a morphologically-distinct retina. By performing a comparative analysis of the expression of a panel of 27 homeodomain, basic-helix-loop-helix and Notch pathway genes between embryonic day (E) 8.75 and postnatal day (P) 9, we identified six distinct RPC molecular profiles. At E8.75, the earliest stage assayed, murine RPCs expressed five homeodomain genes and a single neurogenic gene (Pax6, Six3, Six6, Rx, Otx2, Hes1). This early gene expression profile was remarkably similar to that of 'early' RPCs in the amphibian ciliary marginal zone (CMZ), where RPCs are compartmentalised according to developmental stage, and homologs of Pax6, Six3 and Rx are expressed in the 'early' stem cell zone. As development proceeds, expression of additional homeodomain, bHLH and neurogenic genes was gradually initiated in murine RPCs, allowing distinct genetic profiles to also be defined at E9.5, E10.5, E12.5, E15.5 and P0. In addition, RPCs in the postnatal ciliary margin, where retinal stem cells are retained throughout life, displayed a unique molecular signature, expressing all of the early-onset genes as well as several late-onset markers, indicative of a 'mixed' temporal identity. Taken together, the identification of temporal differences in gene expression in mammalian RPCs during pre-neurogenic developmental stages leads to new insights into how regional identities are progressively acquired during development, while comparisons at later stages highlight the dynamic nature of gene expression in temporally distinct RPC pools. PMID:24148613

Dixit, Rajiv; Tachibana, Nobuhiko; Touahri, Yacine; Zinyk, Dawn; Logan, Cairine; Schuurmans, Carol

2014-01-01

304

Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1) GeneExpression in Egyptian Patients with AcuteMyeloid Leukemia  

PubMed Central

Objective: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1) gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients. Materials and Methods: Using quantitative real-time polymerase chain reaction for detection of LYL1 oncogenes, our study was carried out on 39 myeloid leukemia patients including de novo cases, myelodysplastic syndrome (MDS) with transformation, and chronic myelogenous leukemia (CML) in accelerated and blast crisis, in addition to 10 healthy individuals as the reference control. Results: LYL1 expression was increased at least 2 times compared to the controls. The highest expression of this transcription factor was observed in the MDS cases transformed to acute leukemia at 7.3±3.1, p=0.0011. LYL1 expression was found in 68.2%, 75%, and 77.8% of cases of acute myeloid leukemia, CML crisis, and MDS, respectively. Significant correlation of LYL1 overexpression with some subtypes of French-American-British classification was found. There was, for the first time, significant correlation between the blood count at diagnosis and LYL1 expression (p=0.023, 0.002, and 0.031 for white blood cells, hemoglobin, and platelets, respectively). The rate of complete remission was lower with very high levels of LYL1 expression and the risk of relapse increased with higher levels of LYL1 expression, suggesting an unfavorable prognosis for cases with enhanced expression. Conclusion: Overexpression of LYL1 is highly associated with acute myeloid leukemia and shows more expression in MDS with unfavorable prognosis in response to induction chemotherapy. These observations could signal a promising tool for a therapeutic target to basic helix–loop helix protein related to transcription factors, which may improve patient outcome in acute myeloid leukemia, MDS, and CML in blast crisis.

El-Menshawy, Nadia; Shahin, Doaa; Ghazi, Hayam Fathi

2014-01-01

305

Basic lubrication equations  

NASA Technical Reports Server (NTRS)

Lubricants, usually Newtonian fluids, are assumed to experience laminar flow. The basic equations used to describe the flow are the Navier-Stokes equation of motion. The study of hydrodynamic lubrication is, from a mathematical standpoint, the application of a reduced form of these Navier-Stokes equations in association with the continuity equation. The Reynolds equation can also be derived from first principles, provided of course that the same basic assumptions are adopted in each case. Both methods are used in deriving the Reynolds equation, and the assumptions inherent in reducing the Navier-Stokes equations are specified. Because the Reynolds equation contains viscosity and density terms and these properties depend on temperature and pressure, it is often necessary to couple the Reynolds with energy equation. The lubricant properties and the energy equation are presented. Film thickness, a parameter of the Reynolds equation, is a function of the elastic behavior of the bearing surface. The governing elasticity equation is therefore presented.

Hamrock, B. J.; Dowson, D.

1981-01-01

306

Basic Nanotechnology Processes  

NSDL National Science Digital Library

The National Center for Nanotechnology Applications and Career Knowledge (NACK) Center is an organization committed to supporting twoâÂÂyear degree programs in micro and nanotechnology. The center offers online educational material for curriculum enhancement in this subject field. One of these courses focuses on basic nanotechnology processes. The material is a âÂÂhands-on introduction to the processing involved in âÂÂtop downâÂÂ, âÂÂbottom upâÂÂ, and hybrid nanofabrication.â Downloadable features include topics such as introductions to basic pattern transfer, wet etching and uses of plasmas in processing. Additionally, resources on chemical vapor and physical deposition are available in this unit. The site requires a free log-in for access to the material.

2010-03-05

307

Basics of Developing Questionnaires  

NSDL National Science Digital Library

Whether developing questions for questionnaires or interviews or focus groups, there are certain guidelines that help to ensure that respondents provide information that is useful and can later be analyzed. This resource offers advice on developing questions for interviews or focus groups. It contains basics conducting the interviews, providing directions to respondents as well as guidelines for composing the content and wording of the questionnaire. This resource is aimed for use in workshops/conferences and is intended for novice evaluators.

Mcnamara, Carter

308

Population: Basic Statistics  

NSDL National Science Digital Library

This lesson reinforces the idea that Earth's population, including the population of the United States, is gowing at a dramatic rate. It discusses some of the basics of demography, the study of population and its changes, and introduces key terms used to describe a population. The lesson inlcudes an activity in which students use an online reference to look up some population statistics and answer questions related to them.

Rhinehart, Ken; Pratte, John

309

Basic plasma physics II  

Microsoft Academic Search

The basic physics of classical ideal plasmas is presented in reviews of recent theoretical and experimental investigations, with an emphasis on nonlinear interactions violating the assumptions of weak turbulence. Topics examined include Kolmogorov spectra, parametric instabilities in magnetoactive plasmas, collapse and self-focusing of Langmuir waves, collective dissipation and transport, spontaneous reconnection of magnetic-field lines in a collisionless plasma, collective-beam\\/plasma interaction,

A. A. Galeev; R. N. Sudan

1984-01-01

310

Superbug Survival is Basic  

NSDL National Science Digital Library

This on-line news article investigates the question: Can microbial life thrive in the caustic conditions common to floor strippers and baking soda? It reports samples near a landfill in south Chicago that reveal alkaline solutions are basic to certain bacterial superbugs. The article explores the habitat, genetic analysis, and close relatives of these microbial wonders while also conveying that much more research is needed in the area. Useful links are located at the end of the article.

Matsos, Helen; Magazine, Nasa A.

311

Superbug Survival is Basic  

NSDL National Science Digital Library

This on-line news article investigates the question: Can microbial life thrive in the caustic conditions common to floor strippers and baking soda? It reports samples near a landfill in south Chicago that reveal alkaline solutions are basic to certain bacterial superbugs. The article explores the habitat, genetic analysis, and close relatives of these microbial wonders while also conveying that much more research is needed in the area. Useful links are located at the end of the article.

Matsos, Helen

2010-05-06

312

Basics of Space Flight  

NSDL National Science Digital Library

This training module was designed to help the user identify and grasp basic concepts associated with space travel and deep space missions. Separate sections deal with topics such as the physical environment of space (solar system, gravity, orbital mechanics), flight projects (mission concepts, system requirements, design, onboard systems and instruments), and flight operations (launch, cruise, encounter). Links to related topics are embedded in the text.

313

Risk communication basics  

SciTech Connect

In low-trust, high-concern situations, 50% of your credibility comes from perceived empathy and caring, demonstrated in the first 30 s you come in contact with someone. There is no second chance for a first impression. These and other principles contained in this paper provide you with a basic level of understanding of risk communication. The principles identified are time-tested caveats and will assist you in effectively communicating technical information.

Corrado, P.G. [Lawrence Livermore National Laboratory, CA (United States)

1995-12-31

314

The Basic Anaesthesia Machine  

PubMed Central

After WTG Morton's first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey's machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia.

Gurudatt, CL

2013-01-01

315

The basic anaesthesia machine.  

PubMed

After WTG Morton's first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey's machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia. PMID:24249876

Gurudatt, Cl

2013-09-01

316

The Basics of MRI  

NSDL National Science Digital Library

The Basics of MRI is a hypertextbook by Dr. Joseph Hornak of the Rochester Institute of Technology that focuses on the mathematics and physics of magnetic resonance imaging. "Exponential Functions," "Differentials and Integrals," and "Coordinate Transformation" are just a few of the mathematical topics discussed. The physics behind MRI is broken down into the following chapters: "Spin Physics," "NMR Spectroscopy," "Fourier Transforms," "Imaging Principles," and "Fourier Transform Imaging Principles." Hornak has also included a multitude of information on imaging techniques, presentation, and hardware. Those concerned with what occurs during a MRI exam, rather than the math and physics of MRI, will want to consult the chapter entitled "Your MRI Exam."

Hornak, Joseph P.

1996-01-01

317

Menstrual Cycle: Basic Biology  

PubMed Central

The basic biology of the menstrual cycle is a complex, coordinated sequence of events involving the hypothalamus, anterior pituitary, ovary, and endometrium. The menstrual cycle with all its complexities can be easily perturbed by environmental factors such as stress, extreme exercise, eating disorders, and obesity. Furthermore, genetic influences such as fragile X premutations (Chapter X), X chromosome abnormalities (Chapter X), and galactose-1-phosphate uridyltransferase (GALT) point mutations (galactosemia) also contribute to perturbations of the menstrual cycle. Although not perfect, mouse model have helped to identify and confirm additional components and pathways in menstrual cycle function and dysfunction in humans.

Hawkins, Shannon M.; Matzuk, Martin M.

2010-01-01

318

Atomic Basic Blocks  

NASA Astrophysics Data System (ADS)

Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

319

Transmission Electron Microscopy Basics  

NSDL National Science Digital Library

This extensive site from the University of Liverpool is a set of resources based on the textbook Transmission Electron Microscopy - Basics by D.B.Williams and C.B.Carter. The tutorial is designed to accompany an introductory course on transmission electron microscopy for students with an understanding of elementary physics. Topics include electron scattering, electron atom interactions, the electron gun, probe size, lenses, depth of field and depth of focus, and others. Each chapter includes interactive Java applets that facilitate understanding of the concepts presented.

Goodhew, Peter; Matter.org

320

Clean Energy Basics  

NSDL National Science Digital Library

From the National Renewable Energy Laboratory, the Clean Energy Basics Website amounts to a good primer on renewable energy. The four sections of the site are each introduced by a question (What is renewable energy? Why is renewable energy important? Why is energy efficiency important? What does clean energy have to do with me?). The What is renewable energy? section is further divided into topics including information and links for solar energy, wind energy, bioenergy, geothermal energy, hydropower, and ocean energy. While many of the links highlighted within the text are internal, there are quite a few links to reliable external sites as well.

321

Career Basics Booklet  

NSDL National Science Digital Library

Struggling with your next career step? Science Careers' editorial team brings you "Career Basics: Advice and Resources for Scientists." The booklet provides advice and help on preparing CVs and resumes, writing grants and scientific papers, networking, and much more. Read each article in the booklet online, or download each chapter or the entire booklet as a PDF. All for free. It is one more tool Science Careers provides to help you jump-start your career, be it in academia or outside the ivory tower!

Science Careers (Science)

2009-01-01

322

Basic facts about Venus  

NASA Technical Reports Server (NTRS)

Because of the disturbing influence of the earth's atmosphere on terrestrial and airborne telescopy, radiometry, thermal mapping, spectroscopy, polarimetry and radar astronomy of Venus, major improvements in the body of theory concerning that planet, began with the Mariner 2 planetary exploration program in 1962. The effect of spacecraft exploration culminated with the influx of data yielded by the Pioneer Venus and Venera 11 and 12 missions of 1978. Attention is presently given to the quantitative enhancement of widely accepted, basic facts about Venus that has resulted from the analysis of space probe data, together with an overview of the major features of past and planned planetary missions.

Colin, L.

1983-01-01

323

Isolation of an Active Lv1 Gene from Cattle Indicates that Tripartite Motif Protein-Mediated Innate Immunity to Retroviral Infection Is Widespread among Mammals  

PubMed Central

Lv1/TRIM5? (tripartite motif 5?) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. Old World monkey TRIM5? blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5? proteins are inactive against HIV-1 but active against divergent murine (N-tropic murine leukemia virus [MLV-N]) and simian (simian immunodeficiency virus from rhesus macaque [SIVmac]) retroviruses, respectively. Here we demonstrate antiviral activity of the first nonprimate TRIM protein, from cattle, active against divergent retroviruses, including HIV-1. The number of closely related human TRIM sequences makes assignment of the bovine sequence as a TRIM5? ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIM5? proteins in the N-terminal RING and B-box 2 domains but significantly less homologous in the C-terminal B30.2 domain, particularly in the region shown to influence antiviral specificity. Intriguingly, some viruses restricted by bovine Lv1, including HIV-1 and MLV-N, are unable to synthesize viral DNA by reverse transcription, whereas restricted HIV-2 makes normal amounts of DNA. The data support the conclusion that TRIM protein-mediated restriction of retroviral infection is a more common attribute of mammals than previously appreciated.

Ylinen, Laura M. J.; Keckesova, Zuzana; Webb, Benjamin L. J.; Gifford, Robert J. M.; Smith, Timothy P. L.; Towers, Greg J.

2006-01-01

324

Protein-Mediated Adhesion of the Dissimilatory Fe(III)-Reducing Bacterium Shewanella alga BrY to Hydrous Ferric Oxide  

PubMed Central

The rate and extent of bacterial Fe(III) mineral reduction are governed by molecular-scale interactions between the bacterial cell surface and the mineral surface. These interactions are poorly understood. This study examined the role of surface proteins in the adhesion of Shewanella alga BrY to hydrous ferric oxide (HFO). Enzymatic degradation of cell surface polysaccharides had no effect on cell adhesion to HFO. The proteolytic enzymes Streptomyces griseus protease and chymotrypsin inhibited the adhesion of S. alga BrY cells to HFO through catalytic degradation of surface proteins. Trypsin inhibited S. alga BrY adhesion solely through surface-coating effects. Protease and chymotrypsin also mediated desorption of adhered S. alga BrY cells from HFO while trypsin did not mediate cell desorption. Protease removed a single peptide band that represented a protein with an apparent molecular mass of 50 kDa. Chymotrypsin removed two peptide bands that represented proteins with apparent molecular masses of 60 and 31 kDa. These proteins represent putative HFO adhesion molecules. S. alga BrY adhesion was inhibited by up to 46% when cells were cultured at sub-MICs of chloramphenicol, suggesting that protein synthesis is necessary for adhesion. Proteins extracted from the surface of S. alga BrY cells inhibited adhesion to HFO by up to 41%. A number of these proteins bound specifically to HFO, suggesting that a complex system of surface proteins mediates S. alga BrY adhesion to HFO.

Caccavo, Frank

1999-01-01

325

Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes  

SciTech Connect

Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipase C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.

Seo, MiRan [Department of Biochemistry and Molecular Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)] [Department of Biochemistry and Molecular Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr [Department of Biochemistry and Molecular Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)] [Department of Biochemistry and Molecular Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2010-03-05

326

Protein-mediated adhesion of the dissimilatory Fe(III)-reducing bacterium Shewanella alga BrY to hydrous ferric oxide  

SciTech Connect

The rate and extent of bacterial Fe(III) mineral reduction are governed by molecular-scale interactions between the bacterial cell surface and the mineral surface. These interactions are poorly understood. This study examined the role of surface proteins in the adhesion of Shewanella alga BrY to hydrous ferric oxide (HFO). Enzymatic degradation of cell surface polysaccharides had no effect on cell adhesion to HFO. The proteolytic enzymes Streptomyces griseus protease and chymotrypsin inhibited the adhesion of S. alga BrY cells to HFO through catalytic degradation of surface proteins. Trypsin inhibited S. alga BrY adhesion solely through surface-coating effects. Protease and chymotrypsin also mediated desorption of adhered S. alga BrY cells from HFO while trypsin did not mediate cell desorption. Protease removed a single peptide band that represented a protein with an apparent molecular mass of 50 kDa. Chymotrypsin removed two peptide bands that represented proteins with apparent molecular masses of 60 and 31 kDa. These proteins represent putative HGO adhesion molecules. A. alga BrY adhesion was inhibited by up to 46% when cells were cultured at sub-MICs of chloramphenicol, suggesting that protein synthesis is necessary for adhesion. Proteins extracted from the surface of S. alga BrY cells inhibited adhesion to HFO by up to 41%. A number of these proteins bound specifically to HFO, suggesting that a complex system of surface proteins mediates S. alga BrY adhesion to HFO.

Caccavo, F. Jr.

1999-11-01

327

Attenuation of G protein-mediated inhibition of N-type calcium currents by expression of caveolins in mammalian NG108-15 cells  

PubMed Central

Caveolins are integral proteins of glycolipid/cholesterol-rich plasmalemmal caveolae domains, where, they may function as a plasma membrane scaffold onto which many classes of signalling molecules, including receptors and heterotrimeric G proteins, can assemble. To ascertain whether caveolins influence G protein-mediated signal transduction, we stably expressed caveolin-1 and ?3 isoforms in the neuroblastoma × glioma NG108–15 hybrid cell line, lacking endogenous caveolins. Subsequently, using whole-cell voltage clamp methods, we examined whether the modulation of N-type voltage-gated Ca2+ channels by Go protein-coupled, ?-type opioid receptors might be affected by recombinant caveolin expression. In transfected NG108–15 cells, caveolins localized at the plasma membrane and, upon subcellular fractionation on sucrose density gradients, they co-localized in Triton-resistant, low buoyancy fractions, with endogenous Go protein ?-subunits. The voltage-dependent inhibition of ?-conotoxin GVIA-sensitive Ba2+ currents following either activation of ?-opioid receptors by the agonist [o-pen2,o-pen5]-enkephalin (DPDPE), or direct stimulation of G proteins with guanosine 5?-O-(thiotriphosphate) (GTP?S) was significantly attenuated in caveolin-expressing cells. The kinetics of Ca2+ channel inhibition were also modified by caveolins. Overall, these results suggest that caveolins may negatively affect G protein-dependent regulation of voltage-gated N-type Ca2+ channels, presumably by causing a reduction of the available pool of activated G proteins.

Toselli, M; Taglietti, V; Parente, V; Flati, S; Pavan, A; Guzzi, F; Parenti, M

2001-01-01

328

Basic space payload fastener  

NASA Technical Reports Server (NTRS)

A new basic space fastener has been developed and tested by the GSFC. The purposes of this fastener are to permit assembly and servicing in space by astronauts and/or robots and to facilitate qualification of payloads on Earth prior to launch by saving time and money during the systems integration and component testing and qualification processes. The space fastener is a rework of the basic machine screw such that crossthreading is impossible; it is self-locking and will not work its way out during launch (vibration proof); it will not wear out despite repeated use; it occupies a small foot print which is comparable to its machine screw equivalent, and it provides force and exhibits strength comparable to its machine screw equivalent. Construction is ultra-simple and cost effective and the principle is applicable across the full range of screw sizes ranging from a #10 screw to 2.5 cm (1 in) or more. In this paper, the fastener principles of operation will be discussed along with test results and construction details. The new fastener also has considerable potential in the commercial sector. A few promising applications will be presented.

Vranish, J. M.; Gorevan, Stephen

1995-01-01

329

Basic and clinical immunology  

NASA Technical Reports Server (NTRS)

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

Chinen, Javier; Shearer, William T.

2003-01-01

330

Basics of NMR  

NSDL National Science Digital Library

Dr. Joseph Hornak of the Rochester Institute of Technology presents this high quality hypertextbook for in-depth coverage of the physics and technique behind Nuclear Magnetic Resonance (NMR) (For Dr. Hornak's Basics of MRI, see the August 4, 1999 Scout Report for Science & Engineering). The material is presented in a detailed and clear manner without over simplifying the concepts. Chapters include "The Mathematics of NMR," "Spin Physics," "NMR Spectroscopy," "Fourier Transforms," "Pulse Sequences," and much more. A chapter on "NMR Hardware" offers an overview of components (like the superconducting magnet and various coils) used in most NMR systems. The "Practical Considerations" chapter emphasizes spectroscopic techniques. With the screen split into two separate frames, explanatory graphics can be viewed alongside the text. A glossary and a list of symbols are also included in this carefully produced textbook.

Hornak, Joseph P.

331

Basic memory module  

NASA Technical Reports Server (NTRS)

Construction and electrical characterization of the 4096 x 2-bit Basic Memory Module (BMM) are reported for the Space Ultrareliable Modular Computer (SUMC) program. The module uses four 2K x 1-bit N-channel FET, random access memory chips, called array chips, and two sense amplifier chips, mounted and interconnected on a ceramic substrate. Four 5% tolerance power supplies are required. At the Module, the address, chip select, and array select lines require a 0-8.5 V MOS signal level. The data output, read-strobe, and write-enable lines operate at TTl levels. Although the module is organized as 4096 x 2 bits, it can be used in a 8196 x 1-bit application with appropriate external connections. A 4096 x 1-bit organization can be obtained by depopulating chips.

Tietze, F. C.

1974-01-01

332

Basics of Electricity  

NSDL National Science Digital Library

This course is one of the quickStep series offered by Siemens in Electricity. These are FREE on-line industrial knowledge building tutorials. quickSTEPs are a great start for industry novices moving into technical jobs or staff in operational support rolls. They can also be very effectively used as out of class assignments for review or to build fundamental skills. Each course includes: an online tutorial organized as a number of units, lessons with self check quiz questions, a glossary of terms, a self-check final exam with scoring, an extensive downloadable PDF, and a study guide. This course focuses on the basics of electricity. The coverage includes: DC circuits, magnetism, alternating current, reactance, impedance, AC circuits and an 88 page study guide.

2008-11-10

333

Basic AC Theory  

NSDL National Science Digital Library

reated by Tony R. Kuphaldt with help from Harvey Lew, Duane Damiano, Mark D. Zarella, John Symonds, and Jason Starck, this chapter of All About Circuit's second volume on Alternating Current describes the basic theory and principles at work. The chapter is divided into six sections: What is alternating current?, AC waveforms, Measurements of AC magnitude, Simple AC circuit calculations, AC phase, and Principles of radio. Each section has clear illustrations and a concise, bulleted review of what was covered at the end. There is also a link to the All About Circuits forums, where contributors and other visitors discuss the material presented. This is an excellent resource for educators in physics and electronic engineering classrooms to introduce lessons or units on alternating current.

Kuphaldt, Tony R.

2008-07-15

334

Basic Concepts of Electricity  

NSDL National Science Digital Library

All About Circuits is a website that âÂÂprovides a series of online textbooks covering electricity and electronics.â Written by Tony R. Kuphaldt, the textbooks available here are wonderful resources for students, teachers, and anyone who is interested in learning more about electronics. This particular section, Basic Concepts of Electricity, is the first chapter in Volume I. Topics covered in this chapter include: static electricity, conductors, insulators, electron flow, electric circuits, voltage, current, and resistance. Diagrams and detailed descriptions of concepts are included throughout the chapter to provide users with a comprehensive lesson. Visitors to the site are also encouraged to discuss concepts and topics using the All About Circuits discussion forums (registration with the site is required to post materials).

Kuphaldt, Tony R.

2008-07-04

335

Basic Business Statistics  

NSDL National Science Digital Library

As business is one of the most popular undergraduate majors in the United States, it stands to reason that there are a number of specialized textbooks and supporting instructional materials that are dedicated to various topics within this field. This particular website is designed to serve as the companion to a basic business statistic textbook published by Prentice Hall, and it contains quizzes, overviews, and other materials that will be helpful to both students of the discipline and educators. The materials here are divided into nineteen chapters that cover topics like sampling, data presentation, linear regression, and decision making. Visitors can also take advantage of the search engine here, which is located at the top right-hand corner of each page.

Berenson, Mark L.

336

Basics of AC Motors  

NSDL National Science Digital Library

This course is one of the quickStep series offered by Siemens in AC Motors. These are FREE on-line industrial knowledge building tutorials. quickSTEPs are a great start for industry novices moving into technical jobs or staff in operational support rolls. They can also be very effectively used as out of class assignments for review or to build fundamental skills. Each course includes: an online tutorial organized as a number of units, lessons with self check quiz questions, a glossary of terms, a self-check final exam with scoring, an extensive downloadable PDF study guide. This course covers: motor basics, NEMA motors, Siemens motorr, final exam, a glossary, plus a 116 page study guide.

2008-11-26

337

Basics of Electrical Products  

NSDL National Science Digital Library

This course is one of the quickStep series offered by Siemens in Electrical Products. These are FREE on-line industrial knowledge building tutorials. quickSTEPs are a great start for industry novices moving into technical jobs or staff in operational support rolls. They can also be very effectively used as out of class assignments for review or to build fundamental skills. Each course includes: -an online tutorial organized as a number of units and lessons with self check quiz questions-a glossary of terms-a self-check final exam with scoring -an extensive downloadable pdf study guideThis course on the basics of electrical products covers residential, commerical, and industrial applications.

2009-06-12

338

Basics of AC Drives  

NSDL National Science Digital Library

This course is one of the quickStep series offered by Siemens in AC Drives. These are FREE on-line industrial knowledge building tutorials. quickSTEPs are a great start for industry novices moving into technical jobs or staff in operational support rolls. They can also be very effectively used as out of class assignments for review or to build fundamental skills. Each course includes: an online tutorial organized as a number of units, lessons with self check quiz questions, a glossary of terms, a self-check final exam with scoring, an extensive downloadable PDF study guide. This course covers AC motor basics, details of the Siemens masterdrive and micromaster, and detailed application notes on torque and horsepower.

2012-12-17

339

Basics of Circuit Breakers  

NSDL National Science Digital Library

This course is one of the quickStep series offered by Siemens in Circuit Breakers. These are FREE on-line industrial knowledge building tutorials. quickSTEPs are a great start for industry novices moving into technical jobs or staff in operational support rolls. They can also be very effectively used as out of class assignments for review or to build fundamental skills. Each course includes: an online tutorial organized as a number of units, lessons with self check quiz questions, a glossary of terms, a self-check final exam with scoring, an extensive downloadable PDF study guide. This course offers: basic concepts, breakers part one, breakers part two, a final exam, a glossary and an 88 page study guide.

2008-11-06

340

Fluid Power Basics  

NSDL National Science Digital Library

Students learn about the fundamental concepts important to fluid power, which includes both pneumatic (gas) and hydraulic (liquid) systems. Both systems contain four basic components: reservoir/receiver, pump/compressor, valve, cylinder. Students learn background information about fluid powerâboth pneumatic and hydraulic systemsâincluding everyday applications in our world (bulldozers, front-end loaders, excavators, chair height lever adjustors, door closer dampers, dental drills, vehicle brakes) and related natural laws. After a few simple teacher demos, they learn about the four components in all fluid power systems, watch two 26-minute online videos about fluid power, complete a crossword puzzle of fluid power terms, and conduct a task card exercise. This prepares them to conduct the associated hands-on activity, using the Portable Fluid Power Demonstrator (teacher-prepared kits) to learn more about the properties of gases and liquids in addition to how forces are transmitted and multiplied within these systems.

Center for Compact and Efficient Fluid Power, College of Agriculture and Biological Engineering,

341

Basic properties and variability  

NASA Technical Reports Server (NTRS)

Giant and supergiant M, S, and C stars are discussed in this survey of research. Basic properties as determined by spectra, chemical composition, photometry, or variability type are discussed. Space motions and space distributions of cool giants are described. Distribution of these stars in our galaxy and those nearby is discussed. Mira variables in particular are surveyed with emphasis on the following topics: (1) phase lag phenomenon; (2) Mira light curves; (3) variations in color indices; (4) determination of multiple periods; (5) correlations between quantities such as period length, light-curve shape, infrared (IR) excess, and visible and IR color diagram; (6) semiregular (SR) variables and different time scales in SR light variations; (7) irregular variable Lb and Lc stars; (8) different time-scale light variations; (9) hydrogen-deficient carbon (HdC) stars, in particular RCB stars; and (10) irreversible changes and rapid evolution in red variable stars.

Querci, Francois R.

1987-01-01

342

Corrosion: Understanding the basics  

SciTech Connect

This new book presents a practical how to approach to understanding and solving the problems of corrosion of structural materials. Although it is written mainly for those having a limited technical background in corrosion, it also provides more experienced engineers with a useful overview of the principles of corrosion and can be used as a general guide for developing a corrosion-control program. Contents include: the effects and economic impact of corrosion; basic concepts important to corrosion; principles of aqueous corrosion; forms of corrosion: recognition and prevention; types of corrosive environments; corrosion characteristics of structural materials; corrosion control by proper design; corrosion control by materials selection; corrosion control by protective coatings and inhibitors; corrosion control by cathodic and anodic protection; corrosion testing and monitoring; techniques for diagnosis of corrosion failures; and glossary of corrosion-related terms.

Davis, J.R. [ed.

2000-07-01

343

Basic and Clinical Neurosciences  

NSDL National Science Digital Library

Columbia University's College of Physicians and Surgeons has been a leader in medical education for over a century, and this website is provided as public service for those in the field of medicine and neuroscience. The website provides a series of lectures and videos that provide a "comprehensive and concise review of the neurosciences." It's best to start by reading the executive summary, and then click on over to the "Topics and Speakers" area. Here visitors can look over several dozen lectures that include "Basic Mechanisms of Pain", "Molecular Genetics", and "Neurobiology of Schizophrenia". The lectures are all of very high quality, and visitors who are seeking additional information should look through the "References and Resources" area for external links to relevant medical organizations, research institutes, and academic departments.

2009-06-05

344

Basic Nanotechnology Processes Laboratory  

NSDL National Science Digital Library

This laboratory course is provided by Nano4Me.org, a product of the National Center for Nanotechnology Applications and Career Knowledge (NACK Center) which is based at the Penn State College of Engineering and is funded through the National Science Foundation's Advanced Technological Education (ATE) program. These twelve labs focus on basic processes in Nanotechnology. Some of the labs are titled Gold Nucleation Analysis, Introduction to LPCVD and PECVD, Introduction to Plasma-based Processing, Liftoff and Surface Modification, and Intro to Scanning Electron Microscopy. These labs can be used in conjunction in a course, or individually as needed by the teacher. Each lab should include an objective, background information, detailed procedure, charts and tables, and follow-up questions. This resource, along with all resources from the NACK Center, require a fast, easy, free log-in to access their materials.

2011-03-08

345

Chronic Pancreatitis (Beyond the Basics)  

MedlinePLUS

... Irritable bowel syndrome (Beyond the Basics) Patient information: Pancreatic cancer (Beyond the Basics) Clinical manifestations and diagnosis of ... of the upper intestine ? An increased risk of pancreatic cancer PANCREATITIS DIAGNOSIS It can be difficult to diagnose ...

346

Basic Tools: Program Listing Processor.  

ERIC Educational Resources Information Center

Presents a program that provides a structured listing of BASIC computer programs in a text file. Indents for-next loops for better appearance and easier understanding. Lists program and provides for several versions of BASIC. (MVL)

Pizarro, Antonio

1988-01-01

347

The Time for Basic Education.  

ERIC Educational Resources Information Center

The author urges school boards to respond to retrenchment by cutting back on all school activities except those necessary to providing a sound, basic education. He presents the Council for Basic Education's definition of this concept. Condensed from "Basic Education", March 1981, p3-5. (Editor/SJL)

Howard, James

1981-01-01

348

Foreign Languages and the Basics.  

ERIC Educational Resources Information Center

This brochure is presented in the context of the "back to basics" movement to draw attention to the fact that the basics of a good education are skills that will enable people to live more effectively in the world of the future and that study of a foreign language contributes to the development of these skills. Basics are defined as abilities,…

Bourque, Jane M.; And Others

349

Zebrafish id2 developmental expression pattern contains evolutionary conserved and species-specific characteristics.  

PubMed

The inhibitor of differentiation or inhibitor of DNA binding (Id) family are members of the helix-loop-helix (HLH) group of transcription factors that play important roles in cell proliferation, differentiation, cell cycle control, and apoptosis. They modulate the formation of active class A-class B basic HLH (bHLH) complexes. Ids lack the amino-terminal associated basic region necessary for DNA binding, thus sequestering the class A factors, inhibiting the formation of active class A-class B heterodimers and, therefore, are considered to act as dominant-negative regulators of differentiation pathways. We isolated zebrafish id2, and its expression during development was characterized. id2, in addition to regions of expression detected in Xenopus and mice, is also expressed in the tegmentum; midbrain-hindbrain boundary; cerebellum; rhombomeres 2,3,4,6; notochord; and corpuscles of Stannius. Furthermore, we show that expression of id2 is repressed in mind bomb mutants, suggesting a role of Notch upstream of Id2. PMID:16252281

Chong, Shang-Wei; Nguyen, Thi-Thu-Hang; Chu, Lee-Thean; Jiang, Yun-Jin; Korzh, Vladimir

2005-12-01

350

Transcriptional plasticity through differential assembly of a multiprotein activation complex.  

PubMed

Cell adaptation to the environment often involves induction of complex gene expression programs under the control of specific transcriptional activators. For instance, in response to cadmium, budding yeast induces transcription of the sulfur amino acid biosynthetic genes through the basic-leucine zipper activator Met4, and also launches a program of substitution of abundant glycolytic enzymes by isozymes with a lower content in sulfur. We demonstrate here that transcriptional induction of PDC6, which encodes a pyruvate decarboxylase isoform with low sulfur content, is directly controlled by Met4 and its DNA-binding cofactors the basic-helix-loop-helix protein Cbf1 and the two homologous zinc finger proteins Met31 and Met32. Study of Cbf1 and Met31/32 association with PDC6 allowed us to find a new mechanism of recruitment of Met4, which allows PDC6 being differentially regulated compared to sulfur amino acid biosynthetic genes. Our findings provide a new example of mechanism allowing transcriptional plasticity within a regulatory network thanks to a definite toolbox comprising a unique master activator and several dedicated DNA-binding cofactors. We also show evidence suggesting that integration of PDC6 to the Met4 regulon may have occurred recently in the evolution of the Saccharomyces cerevisiae lineage. PMID:20392822

Cormier, Laëtitia; Barbey, Régine; Kuras, Laurent

2010-08-01

351

Association Between Seed Dormancy and Pericarp Color Is Controlled by a Pleiotropic Gene That Regulates Abscisic Acid and Flavonoid Synthesis in Weedy Red Rice  

PubMed Central

Seed dormancy has been associated with red grain color in cereal crops for a century. The association was linked to qSD7-1/qPC7, a cluster of quantitative trait loci for seed dormancy/pericarp color in weedy red rice. This research delimited qSD7-1/qPC7 to the Os07g11020 or Rc locus encoding a basic helix-loop-helix family transcription factor by intragenic recombinants and provided unambiguous evidence that the association arises from pleiotropy. The pleiotropic gene expressed in early developing seeds promoted expression of key genes for biosynthesis of abscisic acid (ABA), resulting in an increase in accumulation of the dormancy-inducing hormone; activated a conserved network of eight genes for flavonoid biosynthesis to produce the pigments in the lower epidermal cells of the pericarp tissue; and enhanced seed weight. Thus, the pleiotropic locus most likely controls the dormancy and pigment traits by regulating ABA and flavonoid biosynthetic pathways, respectively. The dormancy effect could be eliminated by a heat treatment, but could not be completely overcome by gibberellic acid or physical removal of the seed maternal tissues. The dormancy-enhancing alleles differentiated into two groups basically associated with tropical and temperate ecotypes of weedy rice. Of the pleiotropic effects, seed dormancy could contribute most to the weed adaptation. Pleiotropy prevents the use of the dormancy gene to improve resistance of white pericarp cultivars against pre-harvest sprouting through conventional breeding approaches.

Gu, Xing-You; Foley, Michael E.; Horvath, David P.; Anderson, James V.; Feng, Jiuhuan; Zhang, Lihua; Mowry, Chase R.; Ye, Heng; Suttle, Jeffrey C.; Kadowaki, Koh-ichi; Chen, Zongxiang

2011-01-01

352

Contrasting patterns of expression of transcription factors in pancreatic ? and ? cells  

PubMed Central

Pancreatic ? and ? cells are derived from the same progenitors but play opposing roles in the control of glucose homeostasis. Disturbances in their function are associated with diabetes mellitus. To identify many of the proteins that define their unique pathways of differentiation and functional features, we have analyzed patterns of gene expression in ?TC1.6 vs. MIN6 cell lines by using oligonucleotide microarrays. Approximately 9–10% of >11,000 transcripts examined showed significant differences between the two cell types. Of >700 known transcripts enriched in either cell type, transcription factors and their regulators (TFR) was one of the most significantly different categories. Ninety-six members of the basic zipper, basic helix–loop–helix, homeodomain, zinc finger, high mobility group, and other transcription factor families were enriched in ? cells; in contrast, homeodomain proteins accounted for 51% of a total of 45 TFRs enriched in ? cells. Our analysis thus highlights fundamental differences in expression of TFR subtypes within these functionally distinct islet cell types. Interestingly, the ? cells appear to express a large proportion of factors associated with progenitor or stem-type cells, perhaps reflecting their earlier appearance during pancreatic development. The implications of these findings for a better understanding of ? and ? cell dysfunction in diabetes mellitus are also considered.

Wang, Jie; Webb, Gene; Cao, Yun; Steiner, Donald F.

2003-01-01

353

Developmental expression of COE across the Metazoa supports a conserved role in neuronal cell-type specification and mesodermal development  

PubMed Central

The transcription factor COE (collier/olfactory-1/early B cell factor) is an unusual basic helix–loop–helix transcription factor as it lacks a basic domain and is maintained as a single copy gene in the genomes of all currently analysed non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its proposed ancestral role in the specification of chemosensory neurons and the wealth of functional data from vertebrates and Drosophila, the evolutionary history of the COE gene can be readily investigated. We have examined the ways in which COE expression has diversified among the Metazoa by analysing its expression from representatives of four disparate invertebrate phyla: Ctenophora (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we have studied COE function with knockdown experiments in S. purpuratus, which indicate that COE is likely to be involved in repressing serotonergic cell fate in the apical ganglion of dipleurula larvae. These analyses suggest that COE has played an important role in the evolution of ectodermally derived tissues (likely primarily nervous tissues) and mesodermally derived tissues. Our results provide a broad evolutionary foundation from which further studies aimed at the functional characterisation and evolution of COE can be investigated. Electronic supplementary material The online version of this article (doi:10.1007/s00427-010-0343-3) contains supplementary material, which is available to authorized users.

Meyer, Neva P.; Seaver, Elaine; Pang, Kevin; McDougall, Carmel; Moy, Vanessa N.; Gordon, Kacy; Degnan, Bernard M.; Martindale, Mark Q.; Burke, Robert D.; Peterson, Kevin J.

2010-01-01

354

Gene Expression Profiling of Pulmonary Fibrosis Identifies Twist1 as an Antiapoptotic Molecular "Rectifier" of Growth Factor Signaling  

PubMed Central

Idiopathic pulmonary fibrosis (IPF) is a progressive and typically fatal lung disease. To gain insight into IPF pathogenesis, we performed gene expression profiling of IPF lungs. Twist1, a basic helix-loop-helix protein, was found among the most consistently and highly up-regulated genes and was expressed in nuclei of type II epithelial cells, macrophages, and fibroblasts in IPF lungs. We studied the function of Twist1 in fibroblasts further, because they are the major effector cells in this disease and persist despite an ambient proapoptotic environment. Twist1 was induced by the profibrotic growth factors (GFs) basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor in primary rat lung fibroblasts (RLFs). Suppression of Twist1 expression resulted in decreased RLF accumulation due to increased apoptosis, whereas Twist1 overexpression protected RLFs against several apoptotic stimuli. Addition of platelet-derived growth factor in combination with other GFs led to an increase in proliferation. When Twist1 was depleted, GFs continued to act as mitogens but caused a marked increase in cell death. The increase in apoptosis under basal or growth factor-stimulated conditions was partly mediated by up-regulation of the proapoptotic Bcl-2 family members, Bim and PUMA. These findings indicate that Twist1 promotes survival and accumulation of fibroblasts by shaping their responsiveness to growth factor stimulation. We propose that Twist1 represents one of the factors that promotes pathogenic accumulation of fibroblasts in fibrotic lung disease.

Bridges, Robert S.; Kass, Daniel; Loh, Katrina; Glackin, Carlota; Borczuk, Alain C.; Greenberg, Steven

2009-01-01

355

The Arabidopsis Mediator Subunit MED25 Differentially Regulates Jasmonate and Abscisic Acid Signaling through Interacting with the MYC2 and ABI5 Transcription Factors[C][W][OA  

PubMed Central

Transcriptional regulation plays a central role in plant hormone signaling. At the core of transcriptional regulation is the Mediator, an evolutionarily conserved, multisubunit complex that serves as a bridge between gene-specific transcription factors and the RNA polymerase machinery to regulate transcription. Here, we report the action mechanisms of the MEDIATOR25 (MED25) subunit of the Arabidopsis thaliana Mediator in regulating jasmonate- and abscisic acid (ABA)–triggered gene transcription. We show that during jasmonate signaling, MED25 physically associates with the basic helix-loop-helix transcription factor MYC2 in promoter regions of MYC2 target genes and exerts a positive effect on MYC2-regulated gene transcription. We also show that MED25 physically associates with the basic Leu zipper transcription factor ABA-INSENSITIVE5 (ABI5) in promoter regions of ABI5 target genes and shows a negative effect on ABI5-regulated gene transcription. Our results reveal that underlying the distinct effects of MED25 on jasmonate and ABA signaling, the interaction mechanisms of MED25 with MYC2 and ABI5 are different. These results highlight that the MED25 subunit of the Arabidopsis Mediator regulates a wide range of signaling pathways through selectively interacting with specific transcription factors.

Chen, Rong; Jiang, Hongling; Li, Lin; Zhai, Qingzhe; Qi, Linlin; Zhou, Wenkun; Liu, Xiaoqiang; Li, Hongmei; Zheng, Wenguang; Sun, Jiaqiang; Li, Chuanyou

2012-01-01

356

Attenuation of G protein-mediated inhibition of N-type calcium currents by expression of caveolins in mammalian NG108-15 cells.  

PubMed

1. Caveolins are integral proteins of glycolipid/cholesterol-rich plasmalemmal caveolae domains, where, they may function as a plasma membrane scaffold onto which many classes of signalling molecules, including receptors and heterotrimeric G proteins, can assemble. To ascertain whether caveolins influence G protein-mediated signal transduction, we stably expressed caveolin-1 and -3 isoforms in the neuroblastoma x glioma NG108-15 hybrid cell line, lacking endogenous caveolins. Subsequently, using whole-cell voltage clamp methods, we examined whether the modulation of N-type voltage-gated Ca2+ channels by G(o) protein-coupled, delta-type opioid receptors might be affected by recombinant caveolin expression. 2. In transfected NG108-15 cells, caveolins localized at the plasma membrane and, upon subcellular fractionation on sucrose density gradients, they co-localized in Triton-resistant, low buoyancy fractions, with endogenous G(o) protein alpha-subunits. 3. The voltage-dependent inhibition of omega-conotoxin GVIA-sensitive Ba2+ currents following either activation of delta-opioid receptors by the agonist [o-pen2,o-pen5]-enkephalin (DPDPE), or direct stimulation of G proteins with guanosine 5'-O-(thiotriphosphate) (GTPgammaS) was significantly attenuated in caveolin-expressing cells. The kinetics of Ca2+ channel inhibition were also modified by caveolins. 4. Overall, these results suggest that caveolins may negatively affect G protein-dependent regulation of voltage-gated N-type Ca2+ channels, presumably by causing a reduction of the available pool of activated G proteins. PMID:11600672

Toselli, M; Taglietti, V; Parente, V; Flati, S; Pavan, A; Guzzi, F; Parenti, M

2001-10-15

357

Network basics for telemedicine.  

PubMed

Early telemedicine networks employed dedicated telecommunications circuits (e.g. leased digital lines) in which the sender and receiver were connected by a private circuit. More recently, the Internet has become widely available for general use, including telemedicine. The Internet was engineered to permit network paths to be shared by all users, so data transmission is fundamentally different from traditional, circuit-switched networks. Early telemedicine applications demonstrated the feasibility of Internet Protocol transmission. The basic performance criteria to use in evaluating newer digital communications technologies that carry both voice and data are: (1) bandwidth; (2) packet loss; (3) end-to-end delay; (4) jitter; (5) privacy and security. Network engineering involves performance trade-offs between the hardware, architecture, security and the budget available. A telemedicine application may be running over a network whose design is entirely under the user's control, or the application may employ some part of the Internet whose design is unknown to the user. If an application is not running to satisfaction, then a network engineer should be consulted. PMID:15829050

Gemmill, Jill

2005-01-01

358

Basic concepts of epigenetics  

PubMed Central

Through epigenetic modifications, specific long-term phenotypic consequences can arise from environmental influence on slowly evolving genomic DNA. Heritable epigenetic information regulates nucleosomal arrangement around DNA and determines patterns of gene silencing or active transcription. One of the greatest challenges in the study of epigenetics as it relates to disease is the enormous diversity of proteins, histone modifications and DNA methylation patterns associated with each unique maladaptive phenotype. This is further complicated by a limitless combination of environmental cues that could alter the epigenome of specific cell types, tissues, organs and systems. In addition, complexities arise from the interpretation of studies describing analogous but not identical processes in flies, plants, worms, yeast, ciliated protozoans, tumor cells and mammals. This review integrates fundamental basic concepts of epigenetics with specific focus on how the epigenetic machinery interacts and operates in continuity to silence or activate gene expression. Topics covered include the connection between DNA methylation, methyl-CpG-binding proteins, transcriptional repression complexes, histone residues, histone modifications that mediate gene repression or relaxation, histone core variant stability, H1 histone linker flexibility, FACT complex, nucleosomal remodeling complexes, HP1 and nuclear lamins.

Mazzio, Elizabeth A

2012-01-01

359

Basics of cytology  

PubMed Central

This overview is intended to give a general outline about the basics of Cytopathology. This is a field that is gaining tremendous momentum all over the world due to its speed, accuracy and cost effectiveness. This review will include a brief description about the history of cytology from its inception followed by recent developments. Discussion about the different types of specimens, whether exfoliative or aspiration will be presented with explanation of its rule as a screening and diagnostic test. A brief description of the indications, utilization, sensitivity, specificity, cost effectiveness, speed and accuracy will be carried out. The role that cytopathology plays in early detection of cancer will be emphasized. The ability to provide all types of ancillary studies necessary to make specific diagnosis that will dictate treatment protocols will be demonstrated. A brief description of the general rules of cytomorphology differentiating benign from malignant will be presented. Emphasis on communication between clinicians and pathologist will be underscored. The limitations and potential problems in the form of false positive and false negative will be briefly discussed. Few representative examples will be shown. A brief description of the different techniques in performing fine needle aspirations will be presented. General recommendation for the safest methods and hints to enhance the sensitivity of different sample procurement will be given. It is hoped that this review will benefit all practicing clinicians that may face certain diagnostic challenges requiring the use of cytological material.

Al-Abbadi, Mousa A.

2011-01-01

360

Seizures in Adults (Beyond the Basics)  

MedlinePLUS

... information: Long QT syndrome (The Basics) Patient information: Myoclonus (The Basics) Patient information: Seizures (The Basics) Patient ... High blood pressure emergencies (The Basics) Patient information: Myoclonus (The Basics) Patient information: Time to stop driving? ( ...

361

Tgf?-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves.  

PubMed

Mature heart valves are complex structures consisting of three highly organized extracellular matrix layers primarily composed of collagens, proteoglycans and elastin. Collectively, these diverse matrix components provide all the necessary biomechanical properties for valve function throughout life. In contrast to healthy valves, myxomatous valve disease is the most common cause of mitral valve prolapse in the human population and is characterized by an abnormal abundance of proteoglycans within the valve tri-laminar structure. Despite the clinical significance, the etiology of this phenotype is not known. Scleraxis (Scx) is a basic-helix-loop-helix transcription factor that we previously showed to be required for establishing heart valve structure during remodeling stages of valvulogenesis. In this study, we report that remodeling heart valves from Scx null mice express decreased levels of proteoglycans, particularly chondroitin sulfate proteoglycans (CSPGs), while overexpression in embryonic avian valve precursor cells and adult porcine valve interstitial cells increases CSPGs. Using these systems we further identify that Scx is positively regulated by canonical Tgf?2 signaling during this process and this is attenuated by MAPK activity. Finally, we show that Scx is increased in myxomatous valves from human patients and mouse models, and overexpression in human mitral valve interstitial cells modestly increases proteoglycan expression consistent with myxomatous mitral valve phenotypes. Together, these studies identify an important role for Scx in regulating proteoglycans in embryonic and mature valve cells and suggest that imbalanced regulation could influence myxomatous pathogenesis. PMID:24157418

Barnette, Damien N; Hulin, Alexia; Ahmed, A S Ishtiaq; Colige, Alain C; Azhar, Mohamad; Lincoln, Joy

2013-12-01

362

Neurogenin3 triggers beta-cell differentiation of retinoic acid-derived endoderm cells.  

PubMed Central

Neurogenin3 is a member of the basic helix-loop-helix ('bHLH') family of transcription factors. It plays a crucial role in the commitment of embryonic endoderm into the pancreatic differentiation programme. This factor is considered to act upstream of a cascade of other transcription factors, leading to the fully differentiated endocrine phenotype. Direct observation of the sequential activation of these factors starting from Neurogenin3 had never been demonstrated. By using retinoic acid-derived-endoderm F9 cells as a model, the present study indicates that the ectopic expression of Neurogenin3 is able to start the differentiation pathway of endocrine pancreas. Neurogenin3 triggers the expression of several pancreatic transcription factors following a well defined temporal activation sequence. By reverse transcriptase PCR, immunohistochemistry and RIA, it is shown that stable transfected cells are able to form embryod bodies that produce insulin in response to glucose stimulation. This is the first report of a differentiation event induced by the ectopic expression of a transcription factor in embryonic pluripotent stem cells.

Vetere, Amedeo; Marsich, Eleonora; Di Piazza, Matteo; Koncan, Raffaella; Micali, Fulvio; Paoletti, Sergio

2003-01-01

363

Isolation of a Regulatory Gene of Anthocyanin Biosynthesis in Tuberous Roots of Purple-Fleshed Sweet Potato[OA  

PubMed Central

Many transcriptional factors harboring the R2R3-MYB domain, basic helix-loop-helix domain, or WD40 repeats have been identified in various plant species as regulators of flavonoid biosynthesis in flowers, seeds, and fruits. However, the regulatory elements of flavonoid biosynthesis in underground organs have not yet been elucidated. We isolated the novel MYB genes IbMYB1 and IbMYB2s from purple-fleshed sweet potato (Ipomoea batatas L. Lam. cv Ayamurasaki). IbMYB1 was predominantly expressed in the purple flesh of tuberous roots but was not detected (or only scarcely) in other anthocyanin-containing tissues such as nontuberous roots, stems, leaves, or flowers. IbMYB1 was also expressed in the tuberous roots of other purple-fleshed cultivars but not in those of orange-, yellow-, or white-fleshed cultivars. Although the orange- or yellow-fleshed cultivars contained anthocyanins in the skins of their tuberous roots, we could not detect IbMYB1 transcripts in these tissues. These results suggest that IbMYB1 controls anthocyanin biosynthesis specifically in the flesh of tuberous roots. The results of transient and stable transformation experiments indicated that expression of IbMYB1 alone was sufficient for induction of all structural anthocyanin genes and anthocyanin accumulation in the flesh of tuberous roots, as well as in heterologous tissues or heterologous plant species.

Mano, Hironori; Ogasawara, Fumiaki; Sato, Kazuhito; Higo, Hiromi; Minobe, Yuzo

2007-01-01

364

The c-Myc protein induces cell cycle progression and apoptosis through dimerization with Max.  

PubMed Central

The c-Myc protein (Myc) is involved in cellular transformation and mitogenesis, but is also a potent inducer of programmed cell death, or apoptosis. Whether these apparently opposite functions are mediated through common or distinct molecular mechanisms remains unclear. Myc and its partner protein, Max, dimerize and bind DNA in vitro and in vivo through basic/helix-loop-helix/leucine zipper motifs (bHLH-LZ). By using complementary leucine zipper mutants (termed MycEG and MaxEG), which dimerize efficiently with each other but not with their wild-type partners, we demonstrate that both cell cycle progression and apoptosis in nontransformed rodent fibroblasts are induced by Myc-Max dimers. MycEG or MaxEG alone are inactive, but co-expression restores ability to prevent withdrawal from the cell cycle and to induce cell death upon removal of growth factors. Thus, Myc can control two alternative cell fates through dimerization with a single partner, Max. Images

Amati, B; Littlewood, T D; Evan, G I; Land, H

1993-01-01

365

Induction of neural differentiation by the transcription factor neuroD2.  

PubMed

Pro-neural basic helix loop helix (bHLH) transcription factors are involved in many aspects of normal neuronal development, and over-expression of genes for several of these factors has been shown to induce aspects of neuronal differentiation in cell lines and stem cells. Here we show that over-expression of NeuroD2 (ND2), Neurogenin1 and 2 leads to morphological differentiation of N18-RE-105 neuroblastoma cells and increased expression of synaptic proteins. Particularly ND2 induced neurite formation and increases in the expression of synaptic proteins such as synaptotagmin, that is not expressed normally in this cell type, as well as the redistribution of another synaptic protein, SNAP25, to a cell membrane location. Infection of human neural progenitor cells using adeno associated viral (AAV) vectors also promoted neuronal differentiation. Over-expressing cells demonstrated a significant increase in the neuron specific form of tubulin as well as increased expression of synaptotagmin. Genetic modification of neural progenitor cell with bHLH factors such as ND2 may be a viable strategy to enhance differentiation of these cells into replacement neurons for human disease. PMID:22197973

Messmer, Kirsten; Shen, Wei-Bin; Remington, Mary; Fishman, Paul S

2012-04-01

366

Artificial ligand binding within the HIF2? PAS-B domain of the HIF2 transcription factor  

PubMed Central

The hypoxia-inducible factor (HIF) basic helix–loop–helix Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim (bHLH-PAS) transcription factors are master regulators of the conserved molecular mechanism by which metazoans sense and respond to reductions in local oxygen concentrations. In humans, HIF is critically important for the sustained growth and metastasis of solid tumors. Here, we describe crystal structures of the heterodimer formed by the C-terminal PAS domains from the HIF2? and ARNT subunits of the HIF2 transcription factor, both in the absence and presence of an artificial ligand. Unexpectedly, the HIF2? PAS-B domain contains a large internal cavity that accommodates ligands identified from a small-molecule screen. Binding one of these ligands to HIF2? PAS-B modulates the affinity of the HIF2?:ARNT PAS-B heterodimer in vitro. Given the essential role of PAS domains in forming active HIF heterodimers, these results suggest a presently uncharacterized ligand-mediated mechanism for regulating HIF2 activity in endogenous and clinical settings.

Scheuermann, Thomas H.; Tomchick, Diana R.; Machius, Mischa; Guo, Yan; Bruick, Richard K.; Gardner, Kevin H.

2009-01-01

367

The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter  

PubMed Central

Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor–normal tissues, survivin and DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin. In reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2 promoter. In contrast to the repression, the activation was delayed and varied depending on serum concentrations and cycle blockers. Studies with reporter mutants located, in the survivin promoter, two Sp1 sites that supported DEC1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter. These findings establish that the survivin gene is a transcription target of DEC1, and induction of survivin is at least in part responsible for DEC1 antiapoptosis.

Li, Y; Xie, M; Yang, J; Yang, D; Deng, R; Wan, Y; Yan, B

2014-01-01

368

Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes.  

PubMed

The von Hippel-Lindau gene product (pVHL) targets the alpha subunit of basic helix-loop-helix transcription factor hypoxia-inducible factor (HIF) for proteasomal degradation. Inactivation of pVhl in the mouse germ line results in embryonic lethality, indicating that tight control of Hif-mediated adaptive responses to hypoxia is required for normal development and tissue function. In order to investigate the role of pVhl in T-cell development, we generated mice with thymocyte-specific inactivation of Vhlh resulting in constitutive transcriptional activity of Hif-1, as well as mice with thymocyte-specific repression of Hif-1 in a wild-type and Vhlh-deficient background. Thymi from Vhlh-deficient mice were small due to a severe reduction in the total number of CD4/CD8-double-positive thymocytes which was associated with increased apoptosis in vivo and in vitro. Increased apoptosis was a result of enhanced caspase 8 activity, while Bcl-2 and Bcl-XL transgene expression had little effect on this phenotype. Inactivation of Hif-1 in Vhlh-deficient thymocytes restored thymic cellularity as well as thymocyte viability in vitro. Our data suggest that tight regulation of Hif-1 via pVhl is required for normal thymocyte development and viability and that an increase in Hif-1 transcriptional activity enhances caspase 8-mediated apoptosis in thymocytes. PMID:15456877

Biju, Mangatt P; Neumann, Aaron K; Bensinger, Steven J; Johnson, Randall S; Turka, Laurence A; Haase, Volker H

2004-10-01

369

Coordinated transcriptional regulation of isopentenyl diphosphate biosynthetic pathway enzymes in plastids by phytochrome-interacting factor 5.  

PubMed

All isoprenoids are derived from a common C5 unit, isopentenyl diphosphate (IPP). In plants, IPP is synthesized via two distinct pathways; the cytosolic mevalonate pathway and the plastidial non-mevalonate (MEP) pathway. In this study, we used a co-expression analysis to identify transcription factors that coordinately regulate the expression of multiple genes encoding enzymes in the IPP biosynthetic pathway. Some candidates showed especially strong correlations with multiple genes encoding MEP-pathway enzymes. We report here that phytochrome-interacting factor 5 (PIF5), a basic-helix-loop-helix type transcription factor, functions as a positive regulator of the MEP pathway. Its overexpression in T87 suspension cultured cells resulted in increased accumulation of chlorophylls and carotenoids. Detailed analyses of carotenoids by HPLC indicated that some carotenoid biosynthetic pathways were concomitantly up-regulated, possibly as a result of enhanced IPP metabolic flow. Our results also revealed other PIF family proteins that play different roles from that of PIF5 in IPP metabolism. PMID:24342623

Mannen, Kazuto; Matsumoto, Takuro; Takahashi, Seiji; Yamaguchi, Yuta; Tsukagoshi, Masanori; Sano, Ryosuke; Suzuki, Hideyuki; Sakurai, Nozomu; Shibata, Daisuke; Koyama, Tanetoshi; Nakayama, Toru

2014-01-10

370

Muscle stem cells and model systems for their investigation.  

PubMed

Stem cells are characterized by their clonal ability both to generate differentiated progeny and to undergo self-renewal. Studies of adult mammalian organs have revealed stem cells in practically every tissue. In the adult skeletal muscle, satellite cells are the primary muscle stem cells, responsible for postnatal muscle growth, hypertrophy, and regeneration. In the past decade, several molecular markers have been found that identify satellite cells in quiescent and activated states. However, despite their prime importance, surprisingly little is known about the biology of satellite cells, as their analysis was for a long time hampered by a lack of genetically amenable experimental models where their properties can be dissected. Here, we review how the embryonic origin of satellite cells was discovered using chick and mouse model systems and discuss how cells from other sources can contribute to muscle regeneration. We present evidence for evolutionarily conserved properties of muscle stem cells and their identification in lower vertebrates and in the fruit fly. In Drosophila, muscle stem cells called adult muscle precursors (AMP) can be identified in embryos and in larvae by persistent expression of a myogenic basic helix-loop-helix factor Twist. AMP cells play a crucial role in the Drosophila life cycle, allowing de novo formation and regeneration of adult musculature during metamorphosis. Based on the premise that AMPs represent satellite-like cells of the fruit fly, important insight into the biology of vertebrate muscle stem cells can be gained from genetic analysis in Drosophila. PMID:17948301

Figeac, Nicolas; Daczewska, Malgorzata; Marcelle, Christophe; Jagla, Krzysztof

2007-12-01

371

Cloning of cDNA encoding the nuclear form of chicken sterol response element binding protein-2 (SREBP-2), chromosomal localization, and tissue expression of chicken SREBP-1 and -2 genes.  

PubMed

Sterol regulatory element binding protein-1 and -2 (SREBP-1 and -2) are key transcription factors involved in the biosynthesis of cholesterol and fatty adds. The SREBP have mainly been studied in rodents in which lipogenesis is regulated in both liver and adipose tissue. There is, however, a paucity of information on birds, in which lipogenesis occurs essentially in the liver as in humans. As a prelude to the investigation of the role of SREBP in lipid metabolism regulation in chicken, we sequenced the cDNA, encoding the mature nuclear form of chicken SREBP-2 protein, mapped SREBP-1 and -2 genes and studied their tissue expressions. The predicted chicken SREBP-2 amino acid sequence shows a 77 to 79% identity with human, mouse, and hamster homologues, with a nearly perfect conservation in all the important functional motifs, basic, helix-loop-helix, and leucine zipper (bHLH-Zip) region as well as cleavage sites. As in the human genome, SREBP-1 and SREBP-2 chicken genes are located on two separate chromosomes, respectively microchromosome 14 and macrochromosome 1. Tissue expression data show that SREBP-1 and SREBP-2 are expressed in a wide variety of tissues in chicken. However, unlike SREBP-2, SREBP-1 is expressed preferentially in the liver and uropygial gland, suggesting an important role of SREBP-1 in the regulation of lipogenesis in avian species. PMID:12580245

Assaf, S; Hazard, D; Pitel, F; Morisson, M; Alizadeh, M; Gondret, F; Diot, C; Vignal, A; Douaire, M; Lagarrigue, S

2003-01-01

372

CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells.  

PubMed

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM. PMID:24747072

Komiya, Eriko; Ohnuma, Kei; Yamazaki, Hiroto; Hatano, Ryo; Iwata, Satoshi; Okamoto, Toshihiro; Dang, Nam H; Yamada, Taketo; Morimoto, Chikao

2014-05-16

373

E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells  

PubMed Central

Background E2A gene, which encodes two basic helix–loop–helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive. Methods qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively. Results E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency. Conclusion Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression.

2013-01-01

374

Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium  

PubMed Central

Endocrine cells of the pancreas and the gastrointestinal tract derive from multipotent endodermal stem cells. We have shown previously that the basic helixloop–helix (bHLH) transcription factor neurogenin3 (ngn3) is required for the specification of the endocrine lineage in uncommitted progenitors in the developing pancreas. We investigate herein the expression and the function of ngn3 in the control of endocrine cell development in the intestinal and gastric epithelium. Our results indicate that as in the pancreas, gastrointestinal endocrine cells derive from ngn3-expressing progenitors. Mice homozygous for a null mutation in ngn3 fail to generate any intestinal endocrine cells, and endocrine progenitor cells are lacking. The other main intestinal epithelial cell types differentiate properly. In contrast, in the glandular stomach, the differentiation of the gastrin- (G cells) and somatostatin (D cells)-secreting cells is impaired whereas serotonin- (enterochromaffin EC cells), histamine- (enterochromaffin-like ECL cells) and ghrelin (X/A cells)-expressing cells are still present. Thus, ngn3 is strictly required for endocrine cell fate specification in multipotent intestinal progenitor cells, whereas gastric endocrine development is both ngn3 dependent and independent.

Jenny, Marjorie; Uhl, Celine; Roche, Colette; Duluc, Isabelle; Guillermin, Valerie; Guillemot, Francois; Jensen, Jan; Kedinger, Michele; Gradwohl, Gerard

2002-01-01

375

Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/NeuroD-deficient mice  

PubMed Central

Candidate transcription factors involved in pancreatic endocrine development have been isolated using insulin gene regulation as a paradigm. The cell-type restricted basic helix–loop–helix (bHLH) gene, BETA2/NeuroD, expressed in pancreatic endocrine cells, the intestine, and the brain, activates insulin gene transcription and can induce neurons to differentiate. To understand the importance of BETA2 in pancreatic endocrine cell differentiation, mice lacking a functional BETA2 gene were generated by gene targeting experiments. Mice carrying a targeted disruption of the BETA2 gene developed severe diabetes and died perinatally. Homozygous BETA2 null mice had a striking reduction in the number of insulin-producing ? cells and failed to develop mature islets. Islet morphogenesis appeared to be arrested between E14.5 and E17.5, a period characterized by major expansion of the ? cell population. The presence of severe diabetes in these mice suggests that proper islet structure plays an important role in blood glucose homeostasis. In addition, secretin- and cholecystokinin-producing enteroendocrine cells failed to develop in the absence of BETA2. The absence of these two pancreatic secretagogs may explain the abnormal cellular polarity and inability to secrete zymogen granules in pancreatic acinar exocrine cells. The nervous system appeared to develop normally, despite abundant expression of BETA2 in differentiating neurons. Thus, BETA2 is critical for the normal development of several specialized cell types arising from the gut endoderm.

Naya, Francisco J.; Huang, Hsiang-Po; Qiu, Yuhong; Mutoh, Hiroyuki; DeMayo, Francesco J.; Leiter, Andrew B.; Tsai, Ming-Jer

1997-01-01

376

Evaluation of candidate spermatogonial markers ID4 and GPR125 in testes of adult human cadaveric organ donors.  

PubMed

The optimal markers for human spermatogonial stem cells (SSCs) are not known. Among the genes recently linked to SSCs in mice and other animals are the basic helix-loop-helix transcription factor ID4 and the orphan G-protein-coupled receptor GPR125. While ID4 and GPR125 are considered putative markers for SSCs, they have not been evaluated for coexpression in human tissue. Furthermore, neither the size nor the character of the human spermatogonial populations that express ID4 and GPR125, respectively, are known. A major barrier to addressing these questions is the availability of healthy adult testis tissue from donors with no known reproductive health problems. To overcome this obstacle, we have employed healthy testicular tissue from a novel set of organ donors (n = 16; aged 17-68 years) who were undergoing post-mortem clinical organ procurement. Using immunolabelling, we found that ID4 and GPR125 are expressed on partially overlapping spermatogonial populations and are more broadly expressed in the normal adult human testis. In addition, we found that expression of ID4 remained stable during ageing. These findings suggest that ID4 and GPR125 could be efficacious for identifying previously unrecognized human spermatogonial subpopulations in conjunction with other putative human stem cell markers, both in younger and older donors. PMID:24902969

Sachs, C; Robinson, B D; Andres Martin, L; Webster, T; Gilbert, M; Lo, H-Y; Rafii, S; Ng, C K; Seandel, M

2014-07-01

377

TCP1 Modulates Brassinosteroid Biosynthesis by Regulating the Expression of the Key Biosynthetic Gene DWARF4 in Arabidopsis thaliana[C][W  

PubMed Central

Brassinosteroids (BRs) are essential phytohormones regulating normal plant growth and development. TCP1, a gene thought to be involved in floral organ symmetric control, was identified as a genetic suppressor of a weak BR receptor mutant, bri1-5, in an activation-tagging genetic screen. TCP1 encodes a putative transcription factor possessing a basic helix-loop-helix domain. The dominant allele of TCP1, tcp1-1D, suppresses the defective phenotypes of bri1-5. Overexpression of a dominant-negative form of TCP1, TCP1-SRDX, with a 12–amino acid repressor sequence fused to TCP1 at its C terminus, results in dwarfed plants resembling BR-deficient or insensitive mutants. The defective phenotypes can be rescued by exogenously applied brassinolide but cannot be recovered by auxins, gibberellins, or cytokinins. BR profile assay (quantitative analysis of BR biosynthetic intermediates) strongly suggests that TCP1 expression level positively coordinates with the function of DWARF4 (DWF4), a key enzyme in BR biosynthesis. Real-time RT-PCR analysis further demonstrated that TCP1 regulates the transcription levels of DWF4, and chromatin immunoprecipitation experiments showed that TCP1 indeed interacts with the DWF4 promoter. Confocal microscopy indicated that TCP1 is mainly confined to the nucleus. The expression of TCP1 appears to be regulated by BR levels. These studies demonstrate another level of regulation through which BRs mediate plant growth and development.

Guo, Zhongxin; Fujioka, Shozo; Blancaflor, Elison B.; Miao, Sen; Gou, Xiaoping; Li, Jia

2010-01-01

378

An upstream open reading frame represses expression of Lc, a member of the R/B family of maize transcriptional activators  

SciTech Connect

The R/B genes of maize encode a family of basic helix-loop-helix proteins that determine where and when the anthocyanin-pigment pathway will be expressed in the plant. Previous studies showed that allelic diversity among family members reflects differences in gene expression, specifically in transcription initiation. The authors present evidence that the R gene Lc is under translational control. They demonstrate that the 235-nt transcript leader of Lc represses expression 25- to 30-fold in an in vivo assay. Repression is mediated by the presence in cis of a 38-codon upstream open reading frame. Furthermore, the coding capacity of the upstream open reading frame influences the magnitude of repression. It is proposed that translational control does not contribute to tissue specificity but prevents overexpression of the Lc protein. The diversity of promoter and 5' untranslated leader sequences among the R/B genes provides an opportunity to study the coevolution of transcriptional and translational mechanisms of gene regulation. 36 refs., 5 figs.

Damiani, R.D. Jr.; Wessler, S.R. (Univ. of Georgia, Athens, GA (United States))

1993-09-01

379

Mouse microRNA-124 regulates the expression of Hes1 in P19 cells.  

PubMed

MicroRNAs (miRNAs) belong to a conserved class of small non-coding RNAs that are typically 18-25 nucleotides long. They are found in both animals and plants. These small RNAs can regulate gene expression at translational level by interacting with their target messenger RNAs, and they play an essential role in the development of plants and animals. To date, more than 200 miRNAs have been identified in mammals; however, their mRNA targets have not yet been identified. In this study, we demonstrate that the expression of Hes-1, which is a basic helix-loop-helix transcriptional repressor, is regulated by miRNA-124 in P19 cells. Reduction in the levels of miR-124 mediated by locked nucleic acids resulted in the accumulation of Hes-1 and hindered the retinoic acid-induced neuronal differentiation of P19 cells. Thus, our results indicate that miR-124 regulates the expression of Hes-1 at the post-transcriptional level and is involved in the retinoic acid-induced neuronal differentiation of P19 cells. PMID:20036862

Wang, Chong; Yao, Nan; Lu, Cai-Ling; Li, Dan; Ma, Xu

2010-01-01

380

Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal differentiation of NT2 cells.  

PubMed

MicroRNAs (miRNAs) are phylogenetically widespread small RNAs of 18-25 nucleotides in length, and are found in animals and plants. These small RNAs can regulate gene expression at a translational level through interactions with their target messenger RNAs, and they have a role in the development of Caenorhabditis elegans and plants. Although more than two hundred miRNAs have been found in mammals, their mRNA targets remain to be identified. Here, we demonstrate that the expression of Hes1, basic helix-loop-helix transcriptional repressor, is regulated by miRNA-23 (miR-23) in NT2 cells. miR-23 is almost complementary to part of the coding region, just upstream of the termination codon, of Hes1 mRNA. Reduction in the level of miR-23 by small interfering RNAs resulted in the accumulation of Hes1, and hindered the retinoic-acid-induced neuronal differentiation of NT2 cells. Thus, our results indicate that miR-23 regulates the expression of Hes1 at the post-transcriptional level, and participates in retinoic-acid-induced neuronal differentiation of NT2 cells. PMID:12808467

Kawasaki, Hiroaki; Taira, Kazunari

2003-06-19

381

Conditional deletion of neurogenin-3 using Nkx2.1iCre results in a mouse model for the central control of feeding, activity and obesity.  

PubMed

The ventral hypothalamus acts to integrate visceral and systemic information to control energy balance. The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3) is required for pancreatic ?-cell development and has been implicated in neuronal development in the hypothalamus. Here, we demonstrate that early embryonic hypothalamic inactivation of Ngn3 (also known as Neurog3) in mice results in rapid post-weaning obesity that is associated with hyperphagia and reduced energy expenditure. This obesity is caused by loss of expression of Pomc in Pomc- and Cart-expressing (Pomc/Cart) neurons in the arcuate nucleus, indicating an incomplete specification of anorexigenic first order neurons. Furthermore, following the onset of obesity, both the arcuate and ventromedial hypothalamic nuclei become insensitive to peripheral leptin treatment. This conditional mouse mutant therefore represents a novel model system for obesity that is associated with hyperphagia and underactivity, and sheds new light upon the roles of Ngn3 in the specification of hypothalamic neurons controlling energy balance. PMID:23649822

Anthwal, Neal; Pelling, Michelle; Claxton, Suzanne; Mellitzer, Georg; Collin, Caitlin; Kessaris, Nicoletta; Richardson, William D; Gradwohl, Gérard; Ang, Siew-Lan

2013-09-01

382

The putative transcription factor CaRtg3 is involved in tolerance to cations and antifungal drugs as well as serum-induced filamentation in Candida albicans.  

PubMed

The activated retrograde (RTG) pathway controls transcription of target genes through a heterodimer of transcription factors, Rtg1 and Rtg3, in Saccharomyces cerevisiae. Here, we have identified the sole homologous gene CaRTG3 that encodes a protein of 520 amino acids with characteristics of the basic helix-loop-helix/leucine zipper (bHLH/Zip) family in Candida albicans. Deletion of CaRTG3 results in C. albicans cells being sensitive to high concentrations of calcium and lithium cations as well as sodium dodecyl sulfate and activates the calcium/calcineurin signaling pathway in C. albicans cells. CaRTG3 is also involved in the tolerance of C. albicans cells to the antifungal drugs azoles and terbinafine, but not to the antifungal drugs casponfungin and amphotericin B as well as the cell-wall-damaging reagents Calcoflour White and Congo red. In contrast to ScRtg3, CaRtg3 is not involved in the osmolar response and is constitutively localized in the nucleus. However, deletion of CaRTG3 results in a delay in serum-induced filamentation of C. albicans cells. Therefore, CaRtg3 plays a role in tolerance to cations and antifungal drugs as well as serum-induced filamentation in C. albicans. PMID:24606409

Yan, Hongbo; Zhao, Yunying; Jiang, Linghuo

2014-06-01

383

Rare variants in single-minded 1 (SIM1) are associated with severe obesity  

PubMed Central

Single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor involved in the development and function of the paraventricular nucleus of the hypothalamus. Obesity has been reported in Sim1 haploinsufficient mice and in a patient with a balanced translocation disrupting SIM1. We sequenced the coding region of SIM1 in 2,100 patients with severe, early onset obesity and in 1,680 controls. Thirteen different heterozygous variants in SIM1 were identified in 28 unrelated severely obese patients. Nine of the 13 variants significantly reduced the ability of SIM1 to activate a SIM1-responsive reporter gene when studied in stably transfected cells coexpressing the heterodimeric partners of SIM1 (ARNT or ARNT2). SIM1 variants with reduced activity cosegregated with obesity in extended family studies with variable penetrance. We studied the phenotype of patients carrying variants that exhibited reduced activity in vitro. Variant carriers exhibited increased ad libitum food intake at a test meal, normal basal metabolic rate, and evidence of autonomic dysfunction. Eleven of the 13 probands had evidence of a neurobehavioral phenotype. The phenotypic similarities between patients with SIM1 deficiency and melanocortin 4 receptor (MC4R) deficiency suggest that some of the effects of SIM1 deficiency on energy homeostasis are mediated by altered melanocortin signaling.

Ramachandrappa, Shwetha; Raimondo, Anne; Cali, Anna M.G.; Keogh, Julia M.; Henning, Elana; Saeed, Sadia; Thompson, Amanda; Garg, Sumedha; Bochukova, Elena G.; Brage, Soren; Trowse, Victoria; Wheeler, Eleanor; Sullivan, Adrienne E.; Dattani, Mehul; Clayton, Peter E.; Datta, Vippan; Bruning, John B.; Wareham, Nick J.; O'Rahilly, Stephen; Peet, Daniel J.; Barroso, Ines; Whitelaw, Murray L.; Farooqi, I. Sadaf

2013-01-01

384

bHLH122 is important for drought and osmotic stress resistance in Arabidopsis and in the repression of ABA catabolism.  

PubMed

• Although proteins in the basic helix-loop-helix (bHLH) family are universal transcription factors in eukaryotes, the biological roles of most bHLH family members are not well understood in plants. • The Arabidopsis thaliana bHLH122 transcripts were strongly induced by drought, NaCl and osmotic stresses, but not by ABA treatment. Promoter::GUS analysis showed that bHLH122 was highly expressed in vascular tissues and guard cells. Compared with wild-type (WT) plants, transgenic plants overexpressing bHLH122 displayed greater resistance to drought, NaCl and osmotic stresses. In contrast, the bhlh122 loss-of-function mutant was more sensitive to NaCl and osmotic stresses than were WT plants. • Microarray analysis indicated that bHLH122 was important for the expression of a number of abiotic stress-responsive genes. In electrophoretic mobility shift assay and chromatin immunoprecipitation assays, bHLH122 could bind directly to the G-box/E-box cis-elements in the CYP707A3 promoter, and repress its expression. Further, up-regulation of bHLH122 substantially increased cellular ABA levels. • These results suggest that bHLH122 functions as a positive regulator of drought, NaCl and osmotic signaling. PMID:24261563

Liu, Wenwen; Tai, Huanhuan; Li, Songsong; Gao, Wei; Zhao, Meng; Xie, Chuanxiao; Li, Wen-Xue

2014-03-01

385

BIGPETALp, a bHLH transcription factor is involved in the control of Arabidopsis petal size  

PubMed Central

In Arabidopsis, APETALA1, PISTILLATA, APETALA3 and SEPALLATA interact to form multimeric protein complexes required to specify petal identity. However, the downstream events that lead to petal specific shape and size remain largely unknown. Organ final size can be influenced by cell number or cell expansion or both. To date, no gene that specifically limits petal size by controlling postmitotic cell expansion has been identified. Here we have identified a novel petal-expressed, basic helix-loop-helix encoding gene (BIGPETAL, BPE) that is involved in the control of petal size. BPE is expressed via two mRNAs derived from an alternative splicing event. The BPEub transcript is expressed ubiquitously, whereas the BPEp transcript is preferentially expressed in petals. We demonstrate that BPEp is positively regulated downstream of APETALA3, PISTILLATA, APETALA1 and PISTILLATA3 and is negatively regulated downstream of AGAMOUS. Plants that lack the petal-expressed variant BPEp have larger petals as a result of increased cell size, showing that BPEp interferes with postmitotic cell expansion. BPEp is therefore a part of the network that links the patterning genes to final morphogenesis.

Szecsi, Judit; Joly, Caroline; Bordji, Karim; Varaud, Emilie; Cock, J Mark; Dumas, Christian; Bendahmane, Mohammed

2006-01-01

386

Plant proximity perception dynamically modulates hormone levels and sensitivity in Arabidopsis.  

PubMed

The shade avoidance syndrome (SAS) refers to a set of plant responses initiated after perception by the phytochromes of light enriched in far-red colour reflected from or filtered by neighbouring plants. These varied responses are aimed at anticipating eventual shading from potential competitor vegetation. In Arabidopsis thaliana, the most obvious SAS response at the seedling stage is the increase in hypocotyl elongation. Here, we describe how plant proximity perception rapidly and temporally alters the levels of not only auxins but also active brassinosteroids and gibberellins. At the same time, shade alters the seedling sensitivity to hormones. Plant proximity perception also involves dramatic changes in gene expression that rapidly result in a new balance between positive and negative factors in a network of interacting basic helix-loop-helix proteins, such as HFR1, PAR1, and BIM and BEE factors. Here, it was shown that several of these factors act as auxin- and BR-responsiveness modulators, which ultimately control the intensity or degree of hypocotyl elongation. It was deduced that, as a consequence of the plant proximity-dependent new, dynamic, and local balance between hormone synthesis and sensitivity (mechanistically resulting from a restructured network of SAS regulators), SAS responses are unleashed and hypocotyls elongate. PMID:24609653

Bou-Torrent, Jordi; Galstyan, Anahit; Gallemí, Marçal; Cifuentes-Esquivel, Nicolás; Molina-Contreras, Maria José; Salla-Martret, Mercè; Jikumaru, Yusuke; Yamaguchi, Shinjiro; Kamiya, Yuji; Martínez-García, Jaime F

2014-06-01

387

A light-regulated genetic module was recruited to carpel development in Arabidopsis following a structural change to SPATULA.  

PubMed

A key innovation of flowering plants is the female reproductive organ, the carpel. Here, we show that a mechanism that regulates carpel margin development in the model flowering plant Arabidopsis thaliana was recruited from light-regulated processes. This recruitment followed the loss from the basic helix-loop-helix transcription factor SPATULA (SPT) of a domain previously responsible for its negative regulation by phytochrome. We propose that the loss of this domain was a prerequisite for the light-independent expression in female reproductive tissues of a genetic module that also promotes shade avoidance responses in vegetative organs. Striking evidence for this proposition is provided by the restoration of wild-type carpel development to spt mutants by low red/far-red light ratios, simulating vegetation shade, which we show to occur via phytochrome B, PHYTOCHROME INTERACTING FACTOR4 (PIF4), and PIF5. Our data illustrate the potential of modular evolutionary events to generate rapid morphological change and thereby provide a molecular basis for neo-Darwinian theories that describe this nongradualist phenomenon. Furthermore, the effects shown here of light quality perception on carpel development lead us to speculate on the potential role of light-regulated mechanisms in plant organs that, like the carpel, form within the shade of surrounding tissues. PMID:22851763

Reymond, Mathieu C; Brunoud, Géraldine; Chauvet, Aurélie; Martínez-Garcia, Jaime F; Martin-Magniette, Marie-Laure; Monéger, Françoise; Scutt, Charles P

2012-07-01

388

A Conserved Network of Transcriptional Activators and Repressors Regulates Anthocyanin Pigmentation in Eudicots[C][W][OPEN  

PubMed Central

Plants require sophisticated regulatory mechanisms to ensure the degree of anthocyanin pigmentation is appropriate to myriad developmental and environmental signals. Central to this process are the activity of MYB-bHLH-WD repeat (MBW) complexes that regulate the transcription of anthocyanin genes. In this study, the gene regulatory network that regulates anthocyanin synthesis in petunia (Petunia hybrida) has been characterized. Genetic and molecular evidence show that the R2R3-MYB, MYB27, is an anthocyanin repressor that functions as part of the MBW complex and represses transcription through its C-terminal EAR motif. MYB27 targets both the anthocyanin pathway genes and basic-helix-loop-helix (bHLH) ANTHOCYANIN1 (AN1), itself an essential component of the MBW activation complex for pigmentation. Other features of the regulatory network identified include inhibition of AN1 activity by the competitive R3-MYB repressor MYBx and the activation of AN1, MYB27, and MYBx by the MBW activation complex, providing for both reinforcement and feedback regulation. We also demonstrate the intercellular movement of the WDR protein (AN11) and R3-repressor (MYBx), which may facilitate anthocyanin pigment pattern formation. The fundamental features of this regulatory network in the Asterid model of petunia are similar to those in the Rosid model of Arabidopsis thaliana and are thus likely to be widespread in the Eudicots.

Albert, Nick W.; Davies, Kevin M.; Lewis, David H.; Zhang, Huaibi; Montefiori, Mirco; Brendolise, Cyril; Boase, Murray R.; Ngo, Hanh; Jameson, Paula E.; Schwinn, Kathy E.

2014-01-01

389

Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin  

PubMed Central

The muscle-specific intermediate filament protein, desmin, is one of the earliest myogenic markers whose functional role during myogenic commitment and differentiation is unknown. Sequence comparison of the presently isolated and fully characterized mouse desmin cDNA clones revealed a single domain of polypeptide similarity between desmin and the basic and helix-loop-helix region of members of the myoD family myogenic regulators. This further substantiated the need to search for the function of desmin. Constructs designed to express anti-sense desmin RNA were used to obtain stably transfected C2C12 myoblast cell lines. Several lines were obtained where expression of the anti-sense desmin RNA inhibited the expression of desmin RNA and protein down to basal levels. As a consequence, the differentiation of these myoblasts was blocked; complete inhibition of myoblast fusion and myotube formation was observed. Rescue of the normal phenotype was achieved either by spontaneous revertants, or by overexpression of the desmin sense RNA in the defective cell lines. In several of the cell lines obtained, inhibition of desmin expression was followed by differential inhibition of the myogenic regulators myoD and/or myogenin, depending on the stage and extent of desmin inhibition in these cells. These data suggested that myogenesis is modulated by at least more than one pathway and desmin, which so far was believed to be merely an architectural protein, seems to play a key role in this process.

1994-01-01

390

Interactions of USF and Ku antigen with a human DNA region containing a replication origin.  

PubMed Central

By means of a combination of ion-exchange and sequence-specific affinity chromatography techniques, we have purified to homogeneity two protein complexes binding in a human DNA region (B48) previously recognized to contain a DNA replication origin. The DNA sequence used for the protein purification (B48 binding site) contains a binding site for basic-helix-loop-helix DNA binding proteins. The first complex is composed of two polypeptides of 42- and 44-kDa; its size, heat stability, and target DNA sequence suggest that it corresponds to transcription factor USF; furthermore, the 42-kDa polypeptide is recognized by antibodies raised against 43-kDa-USF. The second complex is represented by equimolar amounts of two proteins of 72 and 87 kDa; microsequencing of the two species indicated that they correspond to the human Ku antigen. In analogy with Ku, they produce a regular pattern of footprints without an apparent sequence-specificity, and their binding can be competed by unspecific DNA provided that it contains free ends. The potential role of B48 binding site and of these cognate proteins in origin activation is discussed. Images

Toth, E C; Marusic, L; Ochem, A; Patthy, A; Pongor, S; Giacca, M; Falaschi, A

1993-01-01

391

Tfe3 expression is closely associated to macrophage terminal differentiation of human hematopoietic myeloid precursors  

SciTech Connect

The MItf-Tfe family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors encodes four family members: MItf, Tfe3, TfeB and TfeC. In vitro, each protein of the family binds DNA in a homo- or heterodimeric form with other family members. Tfe3 is involved in chromosomal translocations recurrent in different tumors and it has been demonstrated, by in vivo studies, that it plays, redundantly with MItf, an important role in the process of osteoclast formation, in particular during the transition from mono-nucleated to multi-nucleated osteoclasts. Since mono-nucleated osteoclasts derive from macrophages we investigated whether Tfe3 might play a role upstream during hematopoietic differentiation. Here we show that Tfe3 is able to induce mono-macrophagic differentiation of U937 cells, in association with a decrease of cell proliferation and an increase of apoptosis. We also show that Tfe3 does not act physiologically during commitment of CD34+ hematopoietic stem cells (HSCs), since it is not able to direct HSCs toward a specific lineage as observed by clonogenic assay, but is a strong actor of terminal differentiation since it allows human primary myeloblasts' maturation toward the macrophage lineage.

Zanocco-Marani, Tommaso [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Vignudelli, Tatiana [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Gemelli, Claudia [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Pirondi, Sara [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Testa, Anna [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Montanari, Monica [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Parenti, Sandra [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Tenedini, Elena [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Grande, Alexis [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy); Ferrari, Sergio [Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, 41100, Modena (Italy)]. E-mail: sergio@unimo.it

2006-12-10

392

An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis  

PubMed Central

Despite having distinct expression patterns and phenotypes in mutant mice, the myogenic regulatory factors Myf5 and MyoD have been considered to be functionally equivalent. Here, we report that these factors have a different response to DNA damage, due to the presence in MyoD and absence in Myf5 of a consensus site for Abl-mediated tyrosine phosphorylation that inhibits MyoD activity in response to DNA damage. Genotoxins failed to repress skeletal myogenesis in MyoD-null embryos; reintroduction of wild-type MyoD, but not mutant Abl phosphorylation-resistant MyoD, restored the DNA-damage-dependent inhibition of muscle differentiation. Conversely, introduction of the Abl-responsive phosphorylation motif converts Myf5 into a DNA-damage-sensitive transcription factor. Gene-dosage-dependent reduction of Abl kinase activity in MyoD-expressing cells attenuated the DNA-damage-dependent inhibition of myogenesis. The presence of a DNA-damage-responsive phosphorylation motif in vertebrate, but not in invertebrate MyoD suggests an evolved response to environmental stress, originated from basic helix–loop–helix gene duplication in vertebrate myogenesis.

Innocenzi, Anna; Latella, Lucia; Messina, Graziella; Simonatto, Marta; Marullo, Fabrizia; Berghella, Libera; Poizat, Coralie; Shu, Chih-Wen; Wang, Jean Y J; Puri, Pier Lorenzo; Cossu, Giulio

2011-01-01

393

BARREN STALK FASTIGIATE1 Is an AT-Hook Protein Required for the Formation of Maize Ears[W][OA  

PubMed Central

Ears are the seed-bearing inflorescences of maize (Zea mays) plants and represent a crucial component of maize yield. The first step in the formation of ears is the initiation of axillary meristems in the axils of developing leaves. In the classic maize mutant barren stalk fastigiate1 (baf1), first discovered in the 1950s, ears either do not form or, if they do, are partially fused to the main stalk. We positionally cloned Baf1 and found that it encodes a transcriptional regulator containing an AT-hook DNA binding motif. Single coorthologs of Baf1 are found in syntenic regions of brachypodium (Brachypodium distachyon), rice (Oryza sativa), and sorghum (Sorghum bicolor), suggesting that the gene is likely present in all cereal species. Protein–protein interaction assays suggest that BAF1 is capable of forming homodimers and heterodimers with other members of the AT-hook family. Another transcriptional regulator required for ear initiation is the basic helix-loop-helix protein BARREN STALK1 (BA1). Genetic and expression analyses suggest that Baf1 is required to reach a threshold level of Ba1 expression for the initiation of maize ears. We propose that Baf1 functions in the demarcation of a boundary region essential for the specification of a stem cell niche.

Gallavotti, Andrea; Malcomber, Simon; Gaines, Craig; Stanfield, Sharon; Whipple, Clinton; Kellogg, Elizabeth; Schmidt, Robert J.

2011-01-01

394

Developmentally regulated synthesis of p8, a stress-associated transcription cofactor, in diapause-destined embryos of Artemia franciscana  

PubMed Central

?Diapause-destined embryos of the crustacean Artemia franciscana arrest as gastrulae, acquire extreme stress tolerance, and enter profound metabolic dormancy. Among genes upregulated at 2 days postfertilization in these embryos is a homologue of p8, a stress-inducible transcription cofactor. Artemia p8 is smaller than vertebrate homologues but shares a basic helix-loop-helix domain and a bipartite nuclear localization signal. Probing of restriction digested DNA on Southern blots indicated a single Artemia p8 gene and 5?-RACE specified 2 transcription start sites. Several putative cis-acting regulatory sequences, including two heat shock elements, appeared upstream of the p8 transcription start site. Artemia p8 mRNA increased sharply at 1 day postfertilization in diapause-destined embryos and then declined, whereas p8 protein appeared 2 days postfertilization and remained relatively constant throughout development, indicating a stable protein. p8 was not detectable in nauplius-destined (nondiapause) Artemia embryos. Immunofluorescent staining revealed p8 within Artemia nuclei. The results support the idea that p8, a known stress-responsive transcription cofactor, mediates gene expression in diapause-destined Artemia embryos. p8 is the first diapause-related transcription factor identified in crustaceans and 1 of only a small number of such proteins identified in any organism undergoing diapause.

Qiu, Zhijun; MacRae, Thomas H.

2007-01-01

395

Hypoxia-Inducible Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) (HIF-1?): Is It a Rare Exception?  

PubMed Central

The aryl hydrocarbon receptor nuclear translocator (ARNT), also designated as hypoxia-inducible factor (HIF)-1?, plays a pivotal role in the adaptive responses to (micro-)environmental stresses such as dioxin exposure and oxygen deprivation (hypoxia). ARNT belongs to the group of basic helix-loop-helix (bHLH)–Per-ARNT-Sim (PAS) transcription factors, which act as heterodimers. ARNT serves as a common binding partner for the aryl hydrocarbon receptor (AhR) as well as HIF-? subunits. HIF-? proteins are regulated in an oxygen-dependent manner, whereas ARNT is generally regarded as constitutively expressed, meaning that neither the arnt mRNA nor the protein level is influenced by hypoxia (despite the name HIF-1?). However, there is emerging evidence that tumor cells derived from different entities are able to upregulate ARNT, especially under low oxygen tension in a cell-specific manner. The objective of this review is therefore to highlight and summarize current knowledge regarding the hypoxia-dependent upregulation of ARNT, which is in sharp contrast to the general point of view described in the literature. Elucidating the mechanism behind this rare cellular attribute will help us to gain new insights into HIF biology and might provide new strategies for anti-cancer therapeutics. In conclusion, putative treatment effects on ARNT should be taken into account while studying the HIF pathway. This step is of great importance when ARNT is intended to serve as a loading control or as a reference.

Mandl, Markus; Depping, Reinhard

2014-01-01

396

FHL family members suppress vascular endothelial growth factor expression through blockade of dimerization of HIF1? and HIF1?.  

PubMed

Four and a half LIM domain (FHL) proteins belong to a family of LIM-only proteins that have been implicated in the development and progression of various types of cancers. However, the role of FHL proteins in tumor angiogenesis remains to be elucidated. Herein, we demonstrate that FHL1-3 decrease the promoter activity and expression of vascular endothelial growth factor (VEGF), the key regulator of angiogenesis in cancer growth and progression as well as an important target gene of the transcription factor hypoxia-inducible factor 1 (HIF1?/HIF1?). FHL1-3 interacted with HIF1? both in vitro and in vivo. A single LIM domain of FHL1 was sufficient for its interaction with HIF1?. FHL1 interacted with the HIF1? region containing basic helix-loop-helix (bHLH) motif and PER-ARNT-SIM domain, both of which aid in dimerization with HIF1? and DNA binding. FHL1-3 inhibited HIF1 transcriptional activity and HIF1-mediated VEGF expression in a hypoxia-independent manner. Moreover, FHL1 blocked HIF1?-HIF1? heterodimerization and HIF1? recruitment to the VEGF promoter. These data suggest that FHL proteins are involved in negative regulation of VEGF possibly by interfering with the dimerization and DNA binding of HIF1 subunits and may play an important role in tumor angiogenesis. PMID:23086815

Lin, Jing; Qin, Xi; Zhu, Ziman; Mu, Jinsong; Zhu, Lingling; Wu, Kuiwu; Jiao, Huabo; Xu, Xiaojie; Ye, Qinong

2012-11-01

397

bHLH-Orange Transcription Factors in Development and Cancer  

PubMed Central

Basic helix-loop-helix (bHLH) proteins are a large superfamily of transcription factors that play critical roles in many physiological processes including cellular differentiation, cell cycle arrest and apoptosis. Based on structural and phylogenetic analysis, mammalian bHLH-Orange (bHLH-O) proteins, which constitute the repressor family of bHLH factors, can be grouped into four subfamilies: Hes, Hey, Helt and Stra13/Dec. In addition to the bHLH domain that mediates DNA-binding and protein dimerization, all members of this family are characterized by a distinctive motif called the “Orange domain” which is present exclusively in these factors. Genetic studies using targeted mutagenesis in mice have revealed essential roles for many bHLH-O genes in embryonic development, cell fate decisions, differentiation of a number of cell types and in apoptosis. Furthermore, growing evidence of crosstalk between bHLH-O proteins with the tumor suppressors p53 and hypoxia-inducible factor, have started to shed light on their possible roles in oncogenesis. Consistently, deregulated expression of several bHLH-O factors is associated with various human cancers. Here, we review the structure and biological functions of bHLH-O factors, and discuss recent studies that suggest a potential role for these factors in tumorigenesis and tumor progression.

Sun, Hong; Ghaffari, Saghi; Taneja, Reshma

2007-01-01

398

Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL  

PubMed Central

Inhibitor of DNA binding protein 4 (ID4) is a member of the dominant-negative basic helix-loop-helix transcription factor family that lacks DNA binding activity and has tumor suppressor function. ID4 promoter methylation has been reported in acute myeloid leukemia and chronic lymphocytic leukemia (CLL), although the expression, function, and clinical relevance of this gene have not been characterized in either disease. We demonstrate that the promoter of ID4 is consistently methylated to various degrees in CLL cells, and increased promoter methylation in a univariable analysis correlates with shortened patient survival. However, ID4 mRNA and protein expression is uniformly silenced in CLL cells irrespective of the degree of promoter methylation. The crossing of ID4+/? mice with E?-TCL1 mice triggers a more aggressive murine CLL as measured by lymphocyte count and inferior survival. Hemizygous loss of ID4 in nontransformed TCL1-positive B cells enhances cell proliferation triggered by CpG oligonucleotides and decreases sensitivity to dexamethasone-mediated apoptosis. Collectively, this study confirms the importance of the silencing of ID4 in murine and human CLL pathogenesis.

Chen, Shih-Shih; Claus, Rainer; Lucas, David M.; Yu, Lianbo; Qian, Jiang; Ruppert, Amy S.; West, Derek A.; Williams, Katie E.; Johnson, Amy J.; Sablitzky, Fred

2011-01-01

399

The Arabidopsis TT2 Gene Encodes an R2R3 MYB Domain Protein That Acts as a Key Determinant for Proanthocyanidin Accumulation in Developing Seed  

PubMed Central

In Arabidopsis, proanthocyanidins specifically accumulate in the endothelium during early seed development. At least three TRANSPARENT TESTA (TT) genes, TT2, TT8, and TTG1, are necessary for the normal expression of several flavonoid structural genes in immature seed, such as DIHYDROFLAVONOL-4-REDUCTASE and BANYULS (BAN). TT8 and TTG1 were characterized recently and found to code for a basic helix-loop-helix domain transcription factor and a WD-repeat–containing protein, respectively. Here the molecular cloning of the TT2 gene was achieved by T-DNA tagging. TT2 encoded an R2R3 MYB domain protein with high similarity to the rice OsMYB3 protein and the maize COLORLESS1 factor. A TT2–green fluorescent protein fusion protein was located mostly in the nucleus, in agreement with the regulatory function of the native TT2 protein. TT2 expression was restricted to the seed during early embryogenesis, consistent with BAN expression and the proanthocyanidin deposition profile. Finally, in gain-of-function experiments, TT2 was able to induce ectopic expression of BAN in young seedlings and roots in the presence of a functional TT8 protein. Therefore, our results strongly suggest that stringent spatial and temporal BAN expression, and thus proanthocyanidin accumulation, are determined at least partially by TT2.

Nesi, Nathalie; Jond, Clarisse; Debeaujon, Isabelle; Caboche, Michel; Lepiniec, Loic

2001-01-01

400

TFBSshape: a motif database for DNA shape features of transcription factor binding sites.  

PubMed

Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors (TFs), proteins recognize DNA as a three-dimensional object. DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein-DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone. PMID:24214955

Yang, Lin; Zhou, Tianyin; Dror, Iris; Mathelier, Anthony; Wasserman, Wyeth W; Gordân, Raluca; Rohs, Remo

2014-01-01

401

An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice.  

PubMed Central

The product of the scl (also called tal-1 or TCL5) gene is a basic domain, helix-loop-helix (bHLH) transcription factor required for the development of hematopoietic cells. Additionally, scl gene disruption and dysregulation, by either chromosomal translocations or a site-specific interstitial deletion whereby 5' regulatory elements of the sil gene become juxtaposed to the body of the scl gene, is associated with T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma. Here we show that an inappropriately expressed scl protein, driven by sil regulatory elements, can cause aggressive T-cell malignancies in collaboration with a misexpressed LMO1 protein, thus recapitulating the situation seen in a subset of human T-cell ALL. Moreover, we show that inappropriately expressed scl can interfere with the development of other tissues derived from mesoderm. Lastly, we show that an scl construct lacking the scl transactivation domain collaborates with misexpressed LMO1, demonstrating that the scl transactivation domain is dispensable for oncogenesis, and supporting the hypothesis that the scl gene product exerts its oncogenic action through a dominant-negative mechanism.

Aplan, P D; Jones, C A; Chervinsky, D S; Zhao, X; Ellsworth, M; Wu, C; McGuire, E A; Gross, K W

1997-01-01

402

?-Catenin Is Required for Hair-Cell Differentiation in the Cochlea.  

PubMed

The development of hair cells in the auditory system can be separated into steps; first, the establishment of progenitors for the sensory epithelium, and second, the differentiation of hair cells. Although the differentiation of hair cells is known to require the expression of basic helix-loop-helix transcription factor, Atoh1, the control of cell proliferation in the region of the developing cochlea that will ultimately become the sensory epithelium and the cues that initiate Atoh1 expression remain obscure. We assessed the role of Wnt/?-catenin in both steps in gain- and loss-of-function models in mice. The canonical Wnt pathway mediator, ?-catenin, controls the expression of Atoh1. Knock-out of ?-catenin inhibited hair-cell, as well as pillar-cell, differentiation from sensory progenitors but was not required to maintain a hair-cell fate once specified. Constitutive activation of ?-catenin expanded sensory progenitors by inducing additional cell division and resulted in the differentiation of extra hair cells. Our data demonstrate that ?-catenin plays a role in cell division and differentiation in the cochlear sensory epithelium. PMID:24806673

Shi, Fuxin; Hu, Lingxiang; Jacques, Bonnie E; Mulvaney, Joanna F; Dabdoub, Alain; Edge, Albert S B

2014-05-01

403

A new class of transcription factors mediates brassinosteroid-regulated gene expression in Arabidopsis.  

PubMed

Brassinosteroids (BRs) signal through a plasma membrane-localized receptor kinase to regulate plant growth and development. We showed previously that a novel protein, BES1, accumulates in the nucleus in response to BRs, where it plays a role in BR-regulated gene expression; however, the mechanism by which BES1 regulates gene expression is unknown. In this study, we dissect BES1 subdomains and establish that BES1 is a transcription factor that binds to and activates BR target gene promoters both in vitro and in vivo. BES1 interacts with a basic helix-loop-helix protein, BIM1, to synergistically bind to E box (CANNTG) sequences present in many BR-induced promoters. Loss-of-function and gain-of-function mutants of BIM1 and its close family members display BR response phenotypes. Thus, BES1 defines a new class of plant-specific transcription factors that cooperate with transcription factors such as BIM1 to regulate BR-induced genes. PMID:15680330

Yin, Yanhai; Vafeados, Dionne; Tao, Yi; Yoshida, Shigeo; Asami, Tadao; Chory, Joanne

2005-01-28

404

Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis  

PubMed Central

Mammalian organogenesis results from the concerted actions of signaling pathways in progenitor cells that induce a hierarchy of regulated transcription factors critical for organ and cell type determination. Here we demonstrate that sustained Notch activity is required for the temporal maintenance of specific cohorts of proliferating progenitors, which underlies the ability to specify late-arising cell lineages during pituitary organogenesis. Conditional deletion of Rbp-J, which encodes the major mediator of the Notch pathway, leads to premature differentiation of progenitor cells, a phenotype recapitulated by loss of the basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late (Pit1) lineage into the early (corticotrope) lineage. Notch signaling is required for maintaining expression of the tissue-specific paired-like homeodomain transcription factor, Prop1, which is required for generation of the Pit1 lineage. Attenuation of Notch signaling is necessary for terminal differentiation in post-mitotic Pit1+ cells, and the Notch-repressed Pit1 target gene, Math3, is specifically required for maturation and proliferation of the GH-producing somatotrope. Thus, sustained Notch signaling in progenitor cells is required to prevent conversion of the late-arising cell lineages to early-born cell lineages, permitting specification of diverse cell types, a strategy likely to be widely used in mammalian organogenesis.

Zhu, Xiaoyan; Zhang, Jie; Tollkuhn, Jessica; Ohsawa, Ryosuke; Bresnick, Emery H.; Guillemot, Francois; Kageyama, Ryoichiro; Rosenfeld, Michael G.

2006-01-01

405

Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility  

PubMed Central

The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process.

Meredith, David M.; Borromeo, Mark D.; Deering, Tye G.; Casey, Bradford H.; Savage, Trisha K.; Mayer, Paul R.; Hoang, Chinh; Tung, Kuang-Chi; Kumar, Manonmani; Shen, Chengcheng; Swift, Galvin H.

2013-01-01

406

Development of pro-angiogenic engineered transcription factors for the treatment of cardiovascular disease.  

PubMed

Gene therapies that use engineered transcription factors to regulate a patient's own endogenous genetic loci offer several advantages over cDNA-based approaches, including the capacity to upregulate all splice variants of a therapeutic gene. Currently, two engineered transcription factors are being developed for use in gene-mediated revascularisation therapies of cardiovascular disease. Both proteins target a powerful, constitutive transcriptional activation module to a defined sequence in the promoter region of vascular endothelial growth factor-A via linkage to an appropriately specific DNA-binding domain, either the basic helix-loop-helix motif of hypoxia-inducible factor-1alpha (HIF-1alpha) or a designed zinc finger protein. Both factors activate the expression of vascular endothelial growth factor-A in cellular studies and induce angiogenesis in animal models of cardiovascular disease. Phase I studies are underway for the HIF-1alpha-based factor and are expected to commence for the zinc finger protein-based factor by the second half of 2004. PMID:15212621

Rebar, Edward J

2004-07-01

407

Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus  

PubMed Central

Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-?) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.

Miller, Clint L.; Anderson, D. Ryan; Kundu, Ramendra K.; Raiesdana, Azad; Nurnberg, Sylvia T.; Diaz, Roxanne; Cheng, Karen; Leeper, Nicholas J.; Chen, Chung-Hsing; Chang, I-Shou; Schadt, Eric E.; Hsiung, Chao Agnes; Assimes, Themistocles L.; Quertermous, Thomas

2013-01-01

408

FLOWERING BHLH transcriptional activators control expression of the photoperiodic flowering regulator CONSTANS in Arabidopsis  

PubMed Central

Many plants monitor day-length changes throughout the year and use the information to precisely regulate the timing of seasonal flowering for maximum reproductive success. In Arabidopsis thaliana, transcriptional regulation of the CONSTANS (CO) gene and posttranslational regulation of CO protein are crucial mechanisms for proper day-length measurement in photoperiodic flowering. Currently, the CYCLING DOF FACTOR proteins are the only transcription factors known to directly regulate CO gene expression, and the mechanisms that directly activate CO transcription have remained unknown. Here we report the identification of four CO transcriptional activators, named FLOWERING BHLH 1 (FBH1), FBH2, FBH3, and FBH4. All FBH proteins are related basic helix–loop–helix-type transcription factors that preferentially bind to the E-box cis-elements in the CO promoter. Overexpression of all FBH genes drastically elevated CO levels and caused early flowering regardless of photoperiod, whereas CO levels were reduced in the fbh quadruple mutants. In addition, FBH1 is expressed in the vascular tissue and bound near the transcription start site of the CO promoter in vivo. Furthermore, FBH homologs in poplar and rice induced CO expression in Arabidopsis. These results indicate that FBH proteins positively regulate CO transcription for photoperiodic flowering and that this mechanism may be conserved in diverse plant species. Our results suggest that the diurnal CO expression pattern is generated by a concert of redundant functions of positive and negative transcriptional regulators.

Ito, Shogo; Song, Young Hun; Josephson-Day, Anna R.; Miller, Ryan J.; Breton, Ghislain; Olmstead, Richard G.; Imaizumi, Takato

2012-01-01

409

Cryptochromes, Phytochromes, and COP1 Regulate Light-Controlled Stomatal Development in Arabidopsis[W  

PubMed Central

In Arabidopsis thaliana, the cryptochrome (CRY) blue light photoreceptors and the phytochrome (phy) red/far-red light photoreceptors mediate a variety of light responses. COP1, a RING motif–containing E3 ubiquitin ligase, acts as a key repressor of photomorphogenesis. Production of stomata, which mediate gas and water vapor exchange between plants and their environment, is regulated by light and involves phyB and COP1. Here, we show that, in the loss-of-function mutants of CRY and phyB, stomatal development is inhibited under blue and red light, respectively. In the loss-of-function mutant of phyA, stomata are barely developed under far-red light. Strikingly, in the loss-of-function mutant of either COP1 or YDA, a mitogen-activated protein kinase kinase kinase, mature stomata are developed constitutively and produced in clusters in both light and darkness. CRY, phyA, and phyB act additively to promote stomatal development. COP1 acts genetically downstream of CRY, phyA, and phyB and in parallel with the leucine-rich repeat receptor-like protein TOO MANY MOUTHS but upstream of YDA and the three basic helix-loop-helix proteins SPEECHLESS, MUTE, and FAMA, respectively. These findings suggest that light-controlled stomatal development is likely mediated through a crosstalk between the cryptochrome-phytochrome-COP1 signaling system and the mitogen-activated protein kinase signaling pathway.

Kang, Chun-Ying; Lian, Hong-Li; Wang, Fang-Fang; Huang, Ji-Rong; Yang, Hong-Quan

2009-01-01

410

RICE SALT SENSITIVE3 Forms a Ternary Complex with JAZ and Class-C bHLH Factors and Regulates Jasmonate-Induced Gene Expression and Root Cell Elongation[C][W  

PubMed Central

Plasticity of root growth in response to environmental cues and stresses is a fundamental characteristic of land plants. However, the molecular basis underlying the regulation of root growth under stressful conditions is poorly understood. Here, we report that a rice nuclear factor, RICE SALT SENSITIVE3 (RSS3), regulates root cell elongation during adaptation to salinity. Loss of function of RSS3 only moderately inhibits cell elongation under normal conditions, but it provokes spontaneous root cell swelling, accompanied by severe root growth inhibition, under saline conditions. RSS3 is preferentially expressed in the root tip and forms a ternary complex with class-C basic helix-loop-helix (bHLH) transcription factors and JASMONATE ZIM-DOMAIN proteins, the latter of which are the key regulators of jasmonate (JA) signaling. The mutated protein arising from the rss3 allele fails to interact with bHLH factors, and the expression of a significant portion of JA-responsive genes is upregulated in rss3. These results, together with the known roles of JAs in root growth regulation, suggest that RSS3 modulates the expression of JA-responsive genes and plays a crucial role in a mechanism that sustains root cell elongation at appropriate rates under stressful conditions.

Toda, Yosuke; Tanaka, Maiko; Ogawa, Daisuke; Kurata, Kyo; Kurotani, Ken-ichi; Habu, Yoshiki; Ando, Tsuyu; Sugimoto, Kazuhiko; Mitsuda, Nobutaka; Katoh, Etsuko; Abe, Kiyomi; Miyao, Akio; Hirochika, Hirohiko; Hattori, Tsukaho; Takeda, Shin

2013-01-01

411

Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.  

PubMed

Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants. PMID:24707045

Chiasson, David M; Loughlin, Patrick C; Mazurkiewicz, Danielle; Mohammadidehcheshmeh, Manijeh; Fedorova, Elena E; Okamoto, Mamoru; McLean, Elizabeth; Glass, Anthony D M; Smith, Sally E; Bisseling, Ton; Tyerman, Stephen D; Day, David A; Kaiser, Brent N

2014-04-01

412

Modes of Retrotransposition of Long Interspersed Element-1 by Environmental Factors  

PubMed Central

Approximately 42% of the human genome is composed of endogenous retroelements, and the major retroelement component, long interspersed element-1 (L1), comprises ?17% of the total genome. A single human cell has more than 5?×?105 copies of L1, 80?100 copies of which are competent for retrotransposition (RTP). Notably, L1 can induce RTP of other retroelements, such as Alu and SVA, and is believed to function as a driving force of evolution. Although L1-RTP during early embryogenesis has been highlighted in the literature, recent observations revealed that L1-RTP also occurs in somatic cells. However, little is known about how environmental factors induce L1-RTP. Here, we summarize our current understanding of the mechanism of L1-RTP in somatic cells. We have focused on the mode of L1-RTP that is dependent on the basic helix–loop–helix/per–arnt–sim (bHLH/PAS) family of transcription factors. Along with the proposed function of bHLH/PAS proteins in environmental adaptation, we discuss the functional linking of L1-RTP and bHLH/PAS proteins for environmental adaptation and evolution.

Ishizaka, Yukihito; Okudaira, Noriyuki; Tamura, Masato; Iijima, Kenta; Shimura, Mari; Goto, Motohito; Okamura, Tadashi

2012-01-01

413

NeuroD1 is required for survival of photoreceptors but not pinealocytes: Results from targeted gene deletion studies  

PubMed Central

NeuroD1 encodes a basic helix-loop-helix (bHLH) transcription factor involved in the development of neural and endocrine structures, including the retina and pineal gland. To determine the effect of NeuroD1 knockout in these tissues, a Cre/loxP recombination strategy was used to target a NeuroD1 floxed gene and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, which is selectively expressed in the pineal gland and retina. At two months of age NeuroD1 cKO retinas have a dramatic reduction in rod- and cone-driven electroretinograms and contain shortened and disorganized outer segments; by four months NeuroD1 cKO retinas are devoid of photoreceptors. In contrast, the NeuroD1 cKO pineal gland appears histologically normal. Microarray analysis of two-month-old NeuroD1 cKO retina and pineal gland identified a subset of genes that were affected 2- to 100-fold; in addition, a small group of genes exhibit altered differential night/day expression. Included in the down-regulated genes are Aipl1, which is necessary to prevent retinal degeneration, and Ankrd33, which is selectively expressed in the outer segments. These findings suggest that NeuroD1 may act through Aipl1 and other genes to maintain photoreceptor homeostasis.

Ochocinska, Margaret J.; Munoz, Estela M.; Veleri, Shobi; Weller, Joan L.; Coon, Steven L.; Pozdeyev, Nikita; Iuvone, P. Michael; Goebbels, Sandra; Furukawa, Takahisa; Klein, David C.

2012-01-01

414

Tal2 expression is induced by all-trans retinoic acid in P19 cells prior to acquisition of neural fate.  

PubMed

TAL2 is a member of the basic helix-loop-helix family and is essential for the normal development of the mouse brain. However, the function of TAL2 during brain development is unclear. P19 cells are pluripotent mouse embryonal carcinoma cells that adopt neural fates upon exposure to all-trans retinoic acid (atRA) and culture in suspension. We found that the expression of Tal2 gene was induced in P19 cells after addition of atRA in suspension culture. Tal2 expression was detected within 3?h after the induction, and had nearly returned to basal levels by 24?h. When GFP-tagged TAL2 (GFP-TAL2) was expressed in P19 cells, we observed GFP-TAL2 in the nucleus. Moreover, we showed that atRA and retinoic acid receptor ? regulated Tal2 expression. These results demonstrate for the first time that atRA induces Tal2 expression in P19 cells, and suggest that TAL2 commits to the acquisition of neural fate in brain development. PMID:24816818

Kobayashi, Takanobu; Komori, Rie; Ishida, Kiyoshi; Kino, Katsuhito; Tanuma, Sei-Ichi; Miyazawa, Hiroshi

2014-01-01

415

ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies.  

PubMed

We describe a previously unreported syndrome characterized by secondary (post-natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract in a highly consanguineous family with six affected children. Homozygosity mapping and exome sequencing revealed a novel homozygous frameshift mutation in the basic helix-loop-helix transcription factor gene ARNT2 (c.1373_1374dupTC) in affected individuals. This mutation results in absence of detectable levels of ARNT2 transcript and protein from patient fibroblasts compared with controls, consistent with nonsense-mediated decay of the mutant transcript and loss of ARNT2 function. We also show expression of ARNT2 within the central nervous system, including the hypothalamus, as well as the renal tract during human embryonic development. The progressive neurological abnormalities, congenital hypopituitarism and post-retinal visual pathway dysfunction in affected individuals demonstrates for the first time the essential role of ARNT2 in the development of the hypothalamo-pituitary axis, post-natal brain growth, and visual and renal function in humans. PMID:24022475

Webb, Emma A; AlMutair, Angham; Kelberman, Daniel; Bacchelli, Chiara; Chanudet, Estelle; Lescai, Francesco; Andoniadou, Cynthia L; Banyan, Abdul; Alsawaid, Al; Alrifai, Muhammad T; Alahmesh, Mohammed A; Balwi, M; Mousavy-Gharavy, Seyedeh N; Lukovic, Biljana; Burke, Derek; McCabe, Mark J; Kasia, Tessa; Kleta, Robert; Stupka, Elia; Beales, Philip L; Thompson, Dorothy A; Chong, W Kling; Alkuraya, Fowzan S; Martinez-Barbera, Juan-Pedro; Sowden, Jane C; Dattani, Mehul T

2013-10-01

416

Diploidy of Drosophila imaginal cells is maintained by a transcriptional repressor encoded by escargot.  

PubMed

The Drosophila escargot (esg) gene encodes a C2-H2-type zinc finger protein that is expressed in the imaginal discs and histoblasts. In some esg mutants, the abdominal histoblasts become polyploid. It has therefore been suggested that the role of esg is to maintain diploidy of the imaginal cells. We show that esg encodes a DNA-binding protein with high affinity for G/ACAGGTG, the consensus-binding sequence for the basic helix-loop-helix (bHLH) family of transcription factors (E2 box). This DNA-binding activity is essential for esg function in vivo as the strong embryonic lethal allele esgVS8 is caused by an amino acid change within the zinc finger region, leading to reduced affinity for DNA. In cultured cells, a heterodimer of the bHLH proteins Scute and Daughterless activates transcription from promoters containing E2 boxes. The esg protein strongly inhibits this activation, suggesting that esg may regulate developmental processes dependent on bHLH proteins. In larvae, esg protein expressed by the heat shock promoter can rescue the polyploid phenotype of abdominal histoblasts, demonstrating that the phenotype is attributable to a loss of esg function. esg must be expressed continuously during the larval period for efficient rescue. Ectopic expression of esg in the salivary glands inhibits endoreplication of DNA. These results suggest that esg is involved in transcriptional inhibition of genes required for endoreplication. PMID:7958894

Fuse, N; Hirose, S; Hayashi, S

1994-10-01

417

scratch, a pan-neural gene encoding a zinc finger protein related to snail, promotes neuronal development.  

PubMed

The Drosophila scratch (scrt) gene is expressed in most or all neuronal precursor cells and encodes a predicted zinc finger transcription factor closely related to the product of the mesoderm determination gene snail (sna). Adult flies homozygous for scrt null alleles have a reduced number of photoreceptors in the eye, and embryos lacking the function of both scrt and the pan-neural gene deadpan (dpn), which encodes a basic helix-loop-helix (bHLH) protein, exhibit a significant loss of neurons. Conversely, ectopic expression of a scrt transgene during embryonic and adult development leads to the production of supernumerary neurons. Consistent with scrt functioning as a transcription factor, various genes are more broadly expressed than normal in scrt null mutants. Reciprocally, these same genes are expressed at reduced levels in response to ectopic scrt expression. We propose that scrt promotes neuronal cell fates by suppressing expression of genes promoting non-neuronal cell fates. We discuss the similarities between the roles of the ancestrally related scrt, sna, and escargot (esc) genes in regulating cell fate choices. PMID:7557390

Roark, M; Sturtevant, M A; Emery, J; Vaessin, H; Grell, E; Bier, E

1995-10-01

418

Snail-type zinc finger proteins prevent neurogenesis in Scutoid and transgenic animals of Drosophila.  

PubMed

Scutoid is a classical dominant gain-of-function mutation of Drosophila, causing a loss of bristles and roughening of the compound eye. Previous genetic and molecular analyses have shown that Scutoid is associated with a chromosomal transposition resulting in a fusion of no-oceli and snail genes. How this gene fusion event leads to the defects in neurogenesis was not known until now. Here have found that snail is ectopically expressed in the eye-antennal and wing imaginal discs in Scutoid larvae, and that this expression is reduced in Scutoid revertants. We have also shown that the expressivity of Scutoid is enhanced by zeste mutations. snail and escargot encode evolutionarily conserved zinc-finger proteins involved in the development of mesoderm and limbs. Snail and Escargot proteins share a common target DNA sequence with the basic helix-loop-helix (bHLH) type proneural gene products. When expressed in the developing external sense organ precursors of the thorax and the eye, these proteins cause a loss of mechanosensory bristles in the thorax and perturbed the development of the compound eye. Such phenotypes resemble those associated with Scutoid. Furthermore, the effect of ectopic Escargot on bristle development is antagonized by coexpression of the bHLH gene asense. Thus, our results suggest that the Scutoid phenotype is due to an ectopic snail expression under the control of no-oceli enhancer, antagonizing neurogenesis through its inhibitory interaction with bHLH proteins. PMID:10552298

Fuse, N; Matakatsu, H; Taniguchi, M; Hayashi, S

1999-10-01

419

Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with Hand2  

PubMed Central

Background The basic Helix-Loop-Helix (bHLH) transcription factor Twist1 fulfills an essential function in neural crest cell formation, migration and survival and is associated with the craniosynostic Saethre-Chotzen syndrome in humans. However, its functions during mandibular development, when it may interact with other bHLH transcription factors like Hand2, are unknown since mice homozygous for the Twist1 null mutation die in early embryogenesis. To determine the role of Twist1 during mandibular development, we used the Hand2-Cre transgene to conditionally inactivate the gene in the neural crest cells populating the mandibular pharyngeal arch. Results The mutant mice exhibited a spectrum of craniofacial anomalies, including mandibular hypoplasia, altered middle ear development, and cleft palate. It appears that Twist1 is essential for the survival of the neural crest cells involved in the development of the mandibular ramal elements. Twist1 plays a role in molar development and cusp formation by participating in the reciprocal signaling needed for the formation of the enamel knot. This gene is also needed to control the ossification of the mandible, a redundant role shared with Hand2. Conclusion Twist1, along with Hand2, is essential for the proximo-distal patterning and development of the mandible and ossification.

Zhang, Yanping; Blackwell, Evan L.; McKnight, Mitchell T.; Knutsen, Gregory R.; Vu, Wendy T.; Ruest, L. Bruno

2012-01-01

420

The mammalian single-minded (SIM) gene: Mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome  

SciTech Connect

We have recently isolated a human homolog (hSIM) of the Drosophila single-minded (sim) gene from the Down syndrome critical region of chromosome 21 using the exon trapping method. The Drosophila sim gene encodes a transcription factor that regulates the development of the central nervous system midline cell lineage. To elucidate the structure of the mammalian SIM protein, we have isolated cDNA clones from a mouse embryo cDNA library. The cDNA clones encode a polypeptide of 657 amino acids with a bHLH (basic-helix-loop-helix) domain, characteristic of a large family of transcription factors, and a PAS (Per-Arnt-Sim) domain in the amino-terminal half region. Both of these domains have striking sequence homology with human SIM and Drosophila SIM proteins. In contrast, the carboxy-terminal half of the mouse SIM protein consists of a proline-rich region with no sequence homology to the Drosophila SIM provator domain of a number of transcription factors. Whole-mount embryo in situ hybridization experiments revealed that the SIM mRNA is expressed prominently in the diencephalon during embryogenesis strongly suggest that the newly isolated mammalian SIM homolog may play a critical role in the development of the mammalian central nervous system. We propose that the human SIM gene may be one of the pathogenic genes of Down syndrome. 36 refs., 6 figs.

Yamaki, Akiko [Keio Univ. School of Medicine, Tokyo (Japan)] [Keio Univ. School of Medicine, Tokyo (Japan); [Kyorin Univ., Tokyo (Japan); Kudoh, Jun; Shindoh, Nobuaki [Keio Univ. School of Medicine, Tokyo (Japan)] [and others] [Keio Univ. School of Medicine, Tokyo (Japan); and others

1996-07-01

421

The Arabidopsis floral homeotic proteins APETALA3 and PISTILLATA negatively regulate the BANQUO genes implicated in light signaling.  

PubMed

The Arabidopsis thaliana MADS box transcription factors APETALA3 (AP3) and PISTILLATA (PI) heterodimerize and are required to specify petal identity, yet many details of how this regulatory process is effected are unclear. We have identified three related genes, BHLH136/BANQUO1 (BNQ1), BHLH134/BANQUO2 (BNQ2), and BHLH161/BANQUO3 (BNQ3), as being directly and negatively regulated by AP3 and PI in petals. BNQ1, BNQ2, and BNQ3 encode products belonging to a family of atypical non-DNA binding basic helix-loop-helix (bHLH) proteins that heterodimerize with and negatively regulate bHLH transcription factors. We show that bnq3 mutants have pale-green sepals and carpels and decreased chlorophyll levels, suggesting that BNQ3 has a role in regulating light responses. The ap3 bnq3 double mutant displays pale second-whorl organs, supporting the hypothesis that BNQ3 is downstream of AP3. Consistent with a role in light response, we show that the BNQ gene products regulate the function of HFR1 (for LONG HYPOCOTYL IN FAR-RED1), which encodes a bHLH protein that regulates photomorphogenesis through modulating phytochrome and cryptochrome signaling. The BNQ genes also are required for appropriate regulation of flowering time. Our results suggest that petal identity is specified in part through downregulation of BNQ-dependent photomorphogenic and developmental signaling pathways. PMID:20305124

Mara, Chloe D; Huang, Tengbo; Irish, Vivian F

2010-03-01

422

ID4: a new player in the cancer arena  

PubMed Central

Id proteins (Id-1 to 4) are dominant negative regulators of basic helix-loop-helix transcription factors. They play a key role during development, preventing cell differentiation while inducing cell proliferation. They are poorly expressed in adult life but can be reactivated in tumorigenesis. Several evidences indicate that Id proteins are associated with loss of differentiation, unrestricted proliferation and neoangiogenesis in diverse human cancers. Recently, we identified Id4 as a transcriptional target of the protein complex mutant p53/E2F1/p300 in breast cancer. Id4 protein binds, stabilizes and enhances the translation of mRNAs encoding proangiogenic cytokines, such as IL8 and GRO-alpha, increasing the angiogenic potential of cancer cells. We present here an overview of the current experimental data that links Id4 to cancer. We provide evidence also of the induction of Id4 following anticancer treatments in mutant p53-carrying cells. Indeed, mutant p53 is recruited to a specific region of the Id4 promoter upon DNA damage. Our findings indicate that Id4, besides its proangiogenic role, might also participate in the chemoresistance associated to mutant p53 proteins exerting gain of function activities.

Dell'Orso, Stefania; Ganci, Federica; Strano, Sabrina; Blandino, Giovanni; Fontemaggi, Giulia

2010-01-01

423

The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development.  

PubMed

GATA and Friend of GATA (FOG) form a transcriptional complex that plays a key role in cardiovascular development in both fish and mammals. In the present study we demonstrate that the basic helix-loop-helix transcription factor Atonal homolog 8 (Atoh8) is required for development of the heart in fish but not in mice. Genetic studies reveal that Atoh8 interacts specifically with Gata4 and Fog1 during development of the heart and swim bladder in the fish. Biochemical studies reveal that ATOH8, GATA4, and FOG2 associate in a single complex in vitro. In contrast to fish, ATOH8-deficient mice exhibit normal cardiac development and loss of ATOH8 does not alter cardiac development in Gata4(+/-) mice. This species difference in the role of ATOH8 is explained in part by LacZ and GFP reporter alleles that reveal restriction of Atoh8 expression to atrial but not ventricular myocardium in the mouse. Our findings identify ATOH8 as a novel regulator of GATA-FOG function that is required for cardiac development in the fish but not the mouse. Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known. PMID:23836893

Rawnsley, David R; Xiao, Jiping; Lee, John S; Liu, Xi; Mericko-Ishizuka, Patricia; Kumar, Vinayak; He, Jie; Basu, Arindam; Lu, MinMin; Lynn, Francis C; Pack, Michael; Gasa, Rosa; Kahn, Mark L

2013-08-23

424

DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis.  

PubMed

DNazymes is a group of catalytic nucleic acids that can be designed to cleave target mRNA molecules in a base-specific way. Twist is a basic helix-loop-helix transcription factor that is involved in the regulation of cellular differentiation and apoptosis. Moreover, it was shown to function in skull development and cause craniosynostosis. DZ-TWT DNazyme was designed to down-regulate Twist expression. The ability of DZ-TWT to cleave mouse Twist mRNA was first shown in a cell-free environment against full-length Twist mRNA. Following transfections of the DZ-TWT in C3H10T1/2 cells, a significant reduction of Twist mRNA levels was observed. This was accompanied by a significant rise in p21 mRNA levels. Finally, DZ-TWT transfections resulted in an increase of cellular apoptosis, demonstrating the importance of Twist in apoptotic pathways. These results prove the usefulness of DNazymes to characterize Twist gene function and further experiments in animals should demonstrate its complete physiological role. PMID:12480539

Hjiantoniou, Eleni; Iseki, Sachiko; Uney, James B; Phylactou, Leonidas A

2003-01-01

425

HES1 Is a Master Regulator of Glucocorticoid Receptor-Dependent Gene Expression  

PubMed Central

Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription factor that is a key regulator of development and organogenesis. However, little is known about the role of HES1 after birth. Glucocorticoids, primary stress hormones that are essential for life, regulate numerous homeostatic processes that permit vertebrates to cope with physiological challenges. The molecular actions of glucocorticoids are mediated by glucocorticoid receptor-dependent regulation of nearly 25% of the genome. We now establish a genome wide molecular link between HES1 and glucocorticoid receptors that controls the ability of cells and animals to respond to stress. Glucocorticoid signaling rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent repression of HES1 was necessary for the glucocorticoid receptor to regulate many of its target genes. Mice with conditional knockout of HES1 in the liver exhibited an expanded glucocorticoid receptor signaling profile and aberrant metabolic phenotype. Our results indicate that HES1 acts as a master repressor, the silencing of which is required for proper glucocorticoid signaling.

Revollo, Javier R.; Oakley, Robert H.; Lu, Nick Z.; Kadmiel, Mahita; Gandhavadi, Maheer; Cidlowski, John A.

2014-01-01

426

Enhanced Generation of Myeloid Lineages in Hematopoietic Differentiation from Embryonic Stem Cells by Silencing Transcriptional Repressor Twist-2  

PubMed Central

Abstract The self-renewal and multilineage differentiation of embryonic stem cells (ESC) is largely governed by transcription factors or repressors. Extensive efforts have focused on elucidating critical factors that control the differentiation of specific cell lineages, for instance, myeloid lineages in hematopoietic development. In this study, we found that Twist-2, a basic helix-loop-helix (bHLH) transcription factor, plays a critical role in inhibiting the differentiation of ESC. Murine ES cells, in which Twist-2 expression is silenced by lentivirally delivered shRNA, exhibit an enhanced formation of primary embryoid bodies (EB) and enhanced differentiation into mesodermally derived hematopoietic colonies. Furthermore, Twist-2 silenced (LV-siTwist-2) ESC display significantly increased generation of myeloid lineages (Gr-1+ and F4/80+ cells) during in vitro hematopoietic differentiation. Treatment with the Toll-like receptor (TLR) 4 ligand synergistically stimulates the generation of primary EB formation as well as of hematopoietic progenitors differentiated from LV-siTwist-2 ES cells. Thus, this study reveals the critical role of the transcriptional repressor Twist-2 in regulating the development of myeloid lineage in hematopoietic differentiation from ESC. This study also suggests a potential strategy for directional differentiation of ESC by inhibiting a transcriptional repressor.

Sharabi, Andrew B.; Lee, Sung-Hyung; Goodell, Margaret A.; Huang, Xue F.

2009-01-01

427

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression  

NASA Astrophysics Data System (ADS)

Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

Makino, Yuichi; Cao, Renhai; Svensson, Kristian; Bertilsson, Göran; Asman, Mikael; Tanaka, Hirotoshi; Cao, Yihai; Berkenstam, Anders; Poellinger, Lorenz

2001-11-01

428

Screening of transcription factors with transcriptional initiation activity.  

PubMed

A majority of mammalian promoters are associated with CpG islands. CpG island promoters frequently lack common core promoter elements, such as the TATA box, and often have dispersed transcription start sites. The mechanism through which CpG island promoters are transcriptionally initiated remains unclear. We speculate that some transcription factors can direct transcription initiation by themselves. To test this hypothesis, we screened a variety of transcription factors to see whether they could initiate transcription. Most transcription factors, including specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), showed little transcriptional initiation activity. However, nuclear respiratory factor 1 (NRF-1), the basic helix-loop-helix/leucine zipper (bHLH/ZIP) family of proteins and the E-twenty six (Ets) family of proteins had strong transcriptional activity. We further demonstrated that these transcription factors initiate dispersed transcription. Our studies provide perspectives to the mechanism of transcription initiation from CpG island promoters. PMID:23933270

Zhang, Lang; Yu, Haoyue; Wang, Pan; Ding, Qingyang; Wang, Zhao

2013-11-15

429

Chimeric Restriction Enzymes: What Is Next?  

PubMed Central

Chimeric restriction enzymes are a novel class of engineered nucleases in which the non-specific DNA cleavage domain of FokI (a type IIS restriction endonuclease) is fused to other DNA-binding motifs. The latter include the three common eukaryotic DNA-binding motifs, namely the helix-turn-helix motif, the zinc finger motif and the basic helix-loop-helix protein containing a leucine zipper motif. Such chimeric nucleases have been shown to make specific cuts in vitro very close to the expected recognition sequences. The most important chimeric nucleases are those based on zinc finger DNA-binding proteins because of their modular structure. Recently, one such chimeric nuclease, Zif-QQR-FN was shown to find and cleave its target in vivo. This was tested by microinjection of DNA substrates and the enzyme into frog oocytes (Carroll et al., 1999). The injected enzyme made site-specific double-strand breaks in the targets even after assembly of the DNA into chromatin. In addition, this cleavage activated the target molecules for efficient homologous recombination. Since the recognition specificity of zinc fingers can be manipulated experimentally, chimeric nucleases could be engineered so as to target a specific site within a genome. The availability of such engineered chimeric restriction enzymes should make it feasible to do genome engineering, also commonly referred to as gene therapy.

Smith, Jeff

2014-01-01

430

NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene.  

PubMed

NeuroD1/beta2 is a basic helix-loop-helix (bHLH) factor expressed in the endocrine cells of the pancreas and in a subset of neurons as they undergo terminal differentiation. We now show that NeuroD1 is expressed in corticotroph cells of the pituitary gland and that it is involved in cell-specific transcription of the proopiomelanocortin (POMC) gene. It was previously shown that corticotroph-specific POMC transcription depends in part on the action of cell-restricted bHLH factors that were characterized as the CUTE (corticotroph upstream transcription element) (M. Therrien and J. Drouin, Mol. Cell. Biol. 13:2342-2353, 1993) complexes. We now demonstrate that these complexes contain NeuroD1 in association with various ubiquitous bHLH dimerization partners. The NeuroD1-containing heterodimers specifically recognize and activate transcription from the POMC promoter E box that confers transcriptional specificity. Interestingly, the NeuroD1 heterodimers activate transcription in synergy with Ptx1, a Bicoid-related homeodomain protein, which also contributes to corticotroph specificity of POMC transcription. In the adult pituitary gland, NeuroD1 transcripts are detected in POMC-expressing corticotroph cells. Taken together with the restricted pattern of Ptx1 expression, these results suggest that these two factors establish the basis of a combinatorial code for the program of corticotroph-specific gene expression. PMID:9343431

Poulin, G; Turgeon, B; Drouin, J

1997-11-01

431

Genetic evidence for pax-3 function in myogenesis in the nematode Pristionchus pacificus.  

PubMed

PAX3 is a member of the PAX3/7 subfamily of the paired box proteins. In vertebrates, Pax3 is essential for skeletal myogenesis by activating a cascade of transcriptional events that are necessary and sufficient for skeletal myogenesis. Four related basic helix-loop-helix transcription factors, MyoD, Myf5, Mrf4, and Myogenin, are targets of PAX3 and serve as myogenic regulatory factors. Although the role of Pax3 in myogenesis is well studied in vertebrates, little is known about invertebrate PAX-3 proteins and myogenesis. Here, we took advantage of viable alleles of pax-3 in the nematode satellite model organism Pristionchus pacificus to investigate the function of PAX-3 in myogenesis. Two strong reduction-of-function alleles of Ppa-pax-3 show severe muscle-derived abnormalities and phalloidin staining indicates a disruption of body wall muscle patterning. Furthermore, we identified a myogenic regulatory factor-related gene Ppa-hlh-1/MyoD and a serum response factor-related gene Ppa-unc-120. Expression of both genes in Ppa-pax-3 mutant animals is down regulated suggesting that Ppa-pax-3 acts upstream in the regulatory network. Together, our results provide the first genetic evidence for a conserved function of PAX-3 in myogenesis between vertebrates and nematodes. PMID:19878288

Yi, Buqing; Bumbarger, Dan; Sommer, Ralf J

2009-01-01

432

The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development  

PubMed Central

During early development of the mouse embryo, expression of the metallothionein-I (MT-I) gene is heightened specifically in the endoderm cells of the visceral yolk sac. The mechanisms of regulation of this cell-specific pattern of expression of metallothionein-I are unknown. However, it has recently been shown that MTF-1, functioning as a metalloregulatory transcription factor, activates metallothionein genes in response to the essential metal zinc. In contrast with the metallothionein genes, MTF-1 is essential for development; null mutant embryos die due to liver degeneration. We report here that MTF-1 is absolutely essential for upregulation of MT-I gene expression in visceral endoderm cells and that optimal expression also involves interactions of the basic helix–loop–helix upstream stimulatory factor-1 (USF1) with an E-box1-containing sequence at –223 bp in the MT-I promoter. Expression of MT-I in visceral endoderm cells was dependent on maternal dietary zinc. Thus, the essential metal, zinc, apparently provides the signaling ligand that activates cell- specific MT-I expression in visceral endoderm cells.

Andrews, Glen K.; Lee, Dae Kee; Ravindra, Rudravajhala; Lichtlen, Peter; Sirito, Mario; Sawadogo, Michele; Schaffner, Walter

2001-01-01

433

MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans  

PubMed Central

In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality.

Riesen, Michele; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M.A.; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F.; Hellberg, Josephine; Thornton, Janet M.; Gems, David

2014-01-01

434

Target-dependent inhibition of sympathetic neuron growth via modulation of a BMP signaling pathway  

PubMed Central

Target-derived factors modulate many aspects of peripheral neuron development including neuronal growth, survival, and maturation. Less is known about how initial target contact regulates changes in gene expression associated with these developmental processes. One early consequence of contact between growing sympathetic neurons and their cardiac myocyte targets is the inhibition of neuronal outgrowth. Analysis of neuronal gene expression following this contact revealed coordinate regulation of a bone morphogenetic protein (BMP)-dependent growth pathway in which basic helix-loop-helix transcription factors and downstream neurofilament expression contribute to the growth dynamics of developing sympathetic neurons. BMP2 had dose-dependent growth promoting effects on sympathetic neurons cultured in the absence, but not the presence, of myocyte targets, suggesting that target contact alters neuronal responses to BMP signaling. Target contact also induced the expression of matrix Gla protein (MGP), a regulator of BMP function in the vascular system. Increased MGP expression inhibited BMP-dependent neuronal growth and MGP expression increased in sympathetic neurons during the period of target contact in vivo. These experiments establish MGP as a novel regulator of BMP function in the nervous system, and define developmental transitions in BMP responses during sympathetic development.

Moon, Jung-Il; Birren, Susan J.

2008-01-01

435

Homozygous Mutations in NEUROD1 Are Responsible for a Novel Syndrome of Permanent Neonatal Diabetes and Neurological Abnormalities  

PubMed Central

OBJECTIVE NEUROD1 is expressed in both developing and mature ?-cells. Studies in mice suggest that this basic helix-loop-helix transcription factor is critical in the development of endocrine cell lineage. Heterozygous mutations have previously been identified as a rare cause of maturity-onset diabetes of the young (MODY). We aimed to explore the potential contribution of NEUROD1 mutations in patients with permanent neonatal diabetes. RESEARCH DESIGN AND METHODS We sequenced the NEUROD1 gene in 44 unrelated patients with permanent neonatal diabetes of unknown genetic etiology. RESULTS Two homozygous mutations in NEUROD1 (c.427_ 428del and c.364dupG) were identified in two patients. Both mutations introduced a frameshift that would be predicted to generate a truncated protein completely lacking the activating domain. Both patients had permanent diabetes diagnosed in the first 2 months of life with no evidence of exocrine pancreatic dysfunction and a morphologically normal pancreas on abdominal imaging. In addition to diabetes, they had learning difficulties, severe cerebellar hypoplasia, profound sensorineural deafness, and visual impairment due to severe myopia and retinal dystrophy. CONCLUSIONS We describe a novel clinical syndrome that results from homozygous loss of function mutations in NEUROD1. It is characterized by permanent neonatal diabetes and a consistent pattern of neurological abnormalities including cerebellar hypoplasia, learning difficulties, sensorineural deafness, and visual impairment. This syndrome highlights the critical role of NEUROD1 in both the development of the endocrine pancreas and the central nervous system in humans.

Rubio-Cabezas, Oscar; Minton, Jayne A.L.; Kantor, Iren; Williams, Denise; Ellard, Sian; Hattersley, Andrew T.

2010-01-01

436

Bhlhb5 is Required for the Subtype Development of Retinal Amacrine and Bipolar Cells in Mice  

PubMed Central

Background BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid–releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5’s functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. Results In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes.

Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

2014-01-01

437

ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE1 (ADPG1), ADPG2, and QUARTET2 Are Polygalacturonases Required for Cell Separation during Reproductive Development in Arabidopsis[W  

PubMed Central

Cell separation is thought to involve degradation of pectin by several hydrolytic enzymes, particularly polygalacturonase (PG). Here, we characterize an activation tagging line with reduced growth and male sterility caused by increased expression of a PG encoded by QUARTET2 (QRT2). QRT2 is essential for pollen grain separation and is part of a small family of three closely related endo-PGs in the Arabidopsis thaliana proteome, including ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE1 (ADPG1) and ADPG2. Functional assays and complementation experiments confirm that ADPG1, ADPG2, and QRT2 are PGs. Genetic analysis demonstrates that ADPG1 and ADPG2 are essential for silique dehiscence. In addition, ADPG2 and QRT2 contribute to floral organ abscission, while all three genes contribute to anther dehiscence. Expression analysis is consistent with the observed mutant phenotypes. INDEHISCENT (IND) encodes a putative basic helix-loop-helix required for silique dehiscence, and we demonstrate that the closely related HECATE3 (HEC3) gene is required for normal seed abscission and show that IND and HEC3 are required for normal expression of ADPG1 in the silique dehiscence zone and seed abscission zone, respectively. We also show that jasmonic acid and ethylene act together with abscisic acid to regulate floral organ abscission, in part by promoting QRT2 expression. These results demonstrate that multiple cell separation events, including both abscission and dehiscence, require closely related PG genes.

Ogawa, Mikihiro; Kay, Pippa; Wilson, Sarah; Swain, Stephen M.

2009-01-01

438

Requirement of the LIM Homeodomain Transcription Factor Tailup for Normal Heart and Hematopoietic Organ Formation in Drosophila melanogaster?  

PubMed Central

Dorsal vessel morphogenesis in Drosophila melanogaster serves as a superb system with which to study the cellular and genetic bases of heart tube formation. We used a cardioblast-expressed Toll-GFP transgene to screen for additional genes involved in heart development and identified tailup as a locus essential for normal dorsal vessel formation. tailup, related to vertebrate islet1, encodes a LIM homeodomain transcription factor expressed in all cardioblasts and pericardial cells of the heart tube as well as in associated lymph gland hematopoietic organs and alary muscles that attach the dorsal vessel to the epidermis. A transcriptional enhancer regulating expression in these four cell types was identified and used as a tailup-GFP transgene with additional markers to characterize dorsal vessel defects resulting from gene mutations. Two reproducible phenotypes were observed in mutant embryos: hypoplastic heart tubes with misaligned cardioblasts and the absence of most lymph gland and pericardial cells. Conversely, a significant expansion of the lymph glands and abnormal morphology of the heart were observed when tailup was overexpressed in the mesoderm. Tailup was shown to bind to two DNA recognition sequences in the dorsal vessel enhancer of the Hand basic helix-loop-helix transcription factor gene, with one site proven to be essential for the lymph gland, pericardial cell, and Svp/Doc cardioblast expression of Hand. Together, these results establish Tailup as being a critical new transcription factor in dorsal vessel morphogenesis and lymph gland formation and place this regulator directly upstream of Hand in these developmental processes.

Tao, Ye; Wang, Jianbo; Tokusumi, Tsuyoshi; Gajewski, Kathleen; Schulz, Robert A.

2007-01-01

439

A posteriori design of crystal contacts to improve the X-ray diffraction properties of a small RNA enzyme  

PubMed Central

The hairpin ribozyme is a small catalytic RNA comprising two helix–loop–helix domains linked by a four-way helical junction (4WJ). In its most basic form, each domain can be formed independently and reconstituted without a 4WJ to yield an active enzyme. The production of such minimal junctionless hairpin ribozymes is achievable by chemical synthesis, which has allowed structures to be determined for numerous nucleotide variants. However, abasic and other destabilizing core modifications hinder crystallization. This investigation describes the use of a dangling 5?-U to form an intermolecular U·U mismatch, as well as the use of synthetic linkers to tether the loop A and B domains, including (i) a three-carbon propyl linker (C3L) and (ii) a nine-atom triethylene glycol linker (S9L). Both linker constructs demonstrated similar enzymatic activity, but S9L constructs yielded crystals that diffracted to 2.65?Å resolution or better. In contrast, C3L variants diffracted to 3.35?Å and exhibited a 15?Å expansion of the c axis. Crystal packing of the C3L construct showed a paucity of 61 contacts, which comprise numerous backbone to 2?-OH hydrogen bonds in junctionless and S9L complexes. Significantly, the crystal packing in minimal structures mimics stabilizing features observed in the 4WJ hairpin ribozyme structure. The results demonstrate how knowledge-based design can be used to improve diffraction and overcome otherwise destabilizing defects.

MacElrevey, Celeste; Spitale, Robert C.; Krucinska, Jolanta; Wedekind, Joseph E.

2007-01-01