The low efficiency observed in cloning by nuclear transfer is related to an aberrant gene expression following errors in epigenetic reprogramming. Recent studies have focused on further understanding of the modifications that take place in the chromatin of embryos during the preimplantation period, through the use of chromatin ...

Aberrant epigenetic nuclear reprogramming results in low somatic cloning efficiency. Altering epigenetic status by applying histone deacetylase inhibitors (HDACi) enhances developmental potential of somatic cell nuclear transfer (SCNT) embryos. The present study was carried out to examine the effects of Oxamflatin, ...

The microRNA (miRNA) genes mir-127 and mir-136 are located near two CpG islands in the imprinted mouse retrotransposon-like gene Rtl1, a key gene involved in placenta formation. These miRNAs appear to be involved in regulating the imprinting of Rtl1. To obtain insights into the epigenetic reprogramming of cloned embryos, we compared the expression levels ...

Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell ...

Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell ...

Somatic cell nuclear transfer (SCNT) has great potential for agricultural applications, generation of medical model animals, transgenic farm animals or generating human embryonic stem cells for treatment of human diseases. Cloned animals derived from somatic cells have been generated in several mammal species, but there are still some unsolved problems with current cloning technology, for example, ...

Abstract The black-footed cat (BFC; Felis nigripes), one of the smallest wild cats, is listed as threatened. Interspecies somatic cell nuclear transfer (Is-SCNT) offers the possibility of preserving endangered species. Development to term of interspecies BFC (Is-BFC) cloned embryos has not been obtained, possibly due to abnormal epigenetic reprogramming. ...

Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as ...

Patient-specific somatic cell reprogramming is likely to have a large impact on medicine by providing a source of cells for disease modelling and regenerative medicine. Several strategies can be used to reprogram cells, yet they are generally characterised by a low reprogramming efficiency, reflecting the remarkable stability of the ...

Epigenetic modifications of the genome are generally stable in somatic cells of multicellular organisms. In germ cells and early embryos, however, epigenetic reprogramming occurs on a genome-wide scale, which includes demethylation of DNA and remodeling of histones and their modifications. The mechanisms of genome-wide erasure of DNA ...

Epigenetic modifications of the genome are generally stable in somatic cells of multicellular organisms. In germ cells and early embryos, however, epigenetic reprogramming occurs on a genome-wide scale, which includes demethylation of DNA and remodeling of histones and their modifications. Mechanisms of genome-wide erasure of DNA ...

Sin3A/B is a master transcriptional scaffold and corepressor that plays an essential role in the regulation of gene transcription and maintenance of chromatin structure, and its inappropriate recruitment has been associated with aberrant gene silencing in cancer. Sin3A/B are highly related, large, multidomian proteins that interact with a wide variety of transcription factors ...

Sin3A/B is a master transcriptional scaffold and corepressor that plays an essential role in the regulation of gene transcription and maintenance of chromatin structure, and its inappropriate recruitment has been associated with aberrant gene silencing in cancer. Sin3A/B are highly related, large, multidomian proteins that interact with a wide variety of transcription factors ...

Loss of genomic imprinting of insulin-like growth factor II (IGF2) is a hallmark of many human neoplasms. We attempted to correct this aberrant epigenotype by transferring nuclei from human tumor cells that showed loss of IGF2 imprinting into enucleated mouse and human fibroblasts that had maintained normal IGF2 imprinting. After nuclear transfer, the abnormal biallelic ...

Epigenetic control of gene regulation is fundamental to the maintenance of cellular identities during all stages of metazoan life. Tissue regeneration involves cellular reprogramming processes, like dedifferentiation, re-differentiation, and trans-differentiation. Hence, in these processes epigenetic maintenance of gene expression ...

Humans are continuously exposed to low-level ionizing radiation from natural sources. However, harsher radiation environments persisted during our planet's early years and mammals survived via an evolutionary gift--a system of radiation-induced natural protective measures (adaptive protection). This system includes antioxidants, DNA repair, apoptosis of severely damaged cells, ...

Humans are continuously exposed to low-level ionizing radiation from natural sources. However, harsher radiation environments persisted during our planet�s early years and mammals survived via an evolutionary gift - a system of radiation-induced natural protective measures (adaptive protection). This system includes antioxidants, DNA repair, apoptosis of severely damaged cells, ...

The cloning of animals by somatic cell nuclear transfer (SCNT) has the potential to allow rapid dissemination of desirable traits from elite animals. However, concern has been expressed that aberrant epigenetic marks in SCNT-derived animals may be passed onto the next generation, even though the offspring of clones appear to be mainly normal. Here, we ...

Despite recent successes in cloning various mammals and amphibians, the low efficiency of animals production and abnormal symptoms in many cloned animals are crucial problems in cloning technology. To overcome these problems, scientists focus on mechanisms of cloning. A possible cause of the low success frequency of cloning is the insufficient dedifferentiation and the inadequate ...

The long-awaited second edition of the International Symposium on "Epigenome Network, Development and Reprogramming of Germ Cells" hosted by Hiroyuki Sasaki took place at the Kyushu University School of Medicine, in Fukuoka, Japan from 22 to 24 November 2010. This meeting brought together again the cr�me de la cr�me of the Japanese research community investigating germline ...

Animal cloning through somatic cell nuclear transfer is very inefficient, probably due to insufficient reprogramming of the donor nuclei, which in turn would cause the dysregulation of gene expression. X-Chromosome inactivation (XCI) is a multi-step epigenetic process utilized by mammals to achieve dosage compensation in females. Our aim was to determine ...

. In turn, the ability to "reprogram" em bryonic development is at the heart of both cloning and stem cell technology. Increasingly, the genetic and the epigenetic, or the molecular 6 #12;BABIES BY DESIGN

Epigenetic reprogramming in the germline provides a developmental model to study the erasure of epigenetic memory as it occurs naturally in vivo in the course of normal embryonic development. Our data show that germline reprogramming comprises both active DNA demethylation and extensive chromatin remodelling that ...

Pluripotent cells can be derived from different types of somatic cells by nuclear reprogramming through the ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc. However, it is unclear whether postmitotic neurons are susceptible to direct reprogramming. Here, we show that postnatal cortical neurons, the vast majority of which are ...

A vast array of successive epigenetic modifications ensures the creation of a healthy individual. Crucial epigenetic reprogramming events occur during germ cell development and early embryogenesis in mammals. As highlighted by the large offspring syndrome with in vitro conceived ovine and bovine animals, any disturbance during germ ...

Epigenetic modifications of DNA such as methylation are important for genome function during development and in adults. DNA methylation has central importance for genomic imprinting and other aspects of epigenetic control of gene expression, and during development methylation patterns are largely maintained in somatic lineages. The mammalian genome ...

Although cloning of mammals has been achieved successfully, the percentage of live offspring is very low because of reduced fetal size and fewer implantation sites. Recent studies have attributed such pathological conditions to abnormal reprogramming of the donor cell used for cloning. The inability of the oocyte to fully restore the differentiated status of a somatic cell to ...

Epigenetic modifications of DNA and chromatin are important for genome function during development and in adults. DNA and chromatin modifications have central importance for genomic imprinting and other aspects of epigenetic control of gene expression. In somatic lineages, modifications are generally stably maintained and are characteristic of different ...

BackgroundBreast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation ...

Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior Michael K determination promotes an epigenetic reprogramming of the male germ-line that is associated Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior. PLoS ONE 3(11): e3745. doi:10

National and international experts will meet at the National Institutes of Health (NIH) on May 30-31, 2002, to present recent advances in epigenetics in human disease. Epigenetics, a new frontier in genetics, focuses on changes in the genome other than DNA mutations that can affect gene expression, such as gene silencing. Epigenetics ...

Epigenetics and Chromatin Remodelling in Development Keystone Resort, Keystone, Colorado, USA 19th This Keystone Symposia meeting on Epigenetics and Chromatin Remodelling in Development was held in the Keystone began was by Azim Surani, well known for his work on imprinting and epigenetic reprogramming. His talk

Experimental studies demonstrated that maternal exposure to certain environmental and dietary factors during early embryonic development can influence the phenotype of offspring as well as the risk of disease development at the later life. DNA methylation, an epigenetic phenomenon, has been suggested as a mechanism by which maternal nutrients affect the phenotype of their ...

Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, ...

SummarySomatic cell nuclear transfer and transcription factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. These two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, by different mechanisms ...

Direct reprogramming of somatic cells to induced pluripotent stem cells by ectopic expression of defined transcription factors has raised fundamental questions regarding the epigenetic stability of the differentiated cell state. In addition, evidence has accumulated that distinct states of pluripotency can interconvert through the modulation of both ...

BackgroundAberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. To assess the extent of abnormal epigenetic modifications and gene expression in clones, we simultaneously examined DNA methylation, histone H4 acetylation and expression of six genes (?-actin, VEGF, oct4, TERT, H19 and ...

Reprogramming of somatic cells to different extents has been reported using different methods. However, this is normally accompanied by the use of exogenous materials, and the overall reprogramming efficiency has been low. Chemicals and small molecules have been used to improve the reprogramming process during somatic cell nuclear ...

Increasing evidence indicates that epigenetic mechanisms are involved in the pathogenesis of autoimmune rheumatic diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The pathogenesis of the organ-specific autoimmune disease psoriasis, however, remains poorly understood. Recent studies have shown that aberrant ...

The production of mature germ cells capable of generating totipotent zygotes is a highly specialized and sexually dimorphic process. The transition from diploid primordial germ cell to haploid spermatozoa requires genome-wide reprogramming of DNA methylation, stage- and testis-specific gene expression, mitotic and meiotic division, and the histone�protamine transition, all ...

Epigenetic reprogramming plays a central role in the development of cloned embryos generated by somatic cell nuclear transfer, and it is believed that aberrant reprogramming leads to the abnormal development of most cloned embryos. Recent studies show that trimethylation of H3K27 (H3K27me3) contributes to the ...

Despite more than a decade of research efforts, farm animal cloning by somatic cell nuclear transfer (SCNT) is still frustratingly inefficient. Inefficiency manifests itself at different levels, which are currently not well integrated. At the molecular level, it leads to widespread genetic, epigenetic and transcriptional aberrations in cloned embryos. At ...

How various layers of epigenetic repression restrict somatic cell nuclear reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional reprogramming of previously repressed genes. Here, we address the mechanisms that restrict reprogramming following ...

The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for ...

Endometrial cancer is the most commonly diagnosed gynecological cancer, and it has been shown to be a complex disease driven by abnormal genetic, and epigenetic alterations, as well as environmental factors. Epigenetic changes resulting in aberrant gene expression are dynamic and modifiable features of many cancer types. A significant ...

Endometrial cancer is the most commonly diagnosed gynecological cancer, and it has been shown to be a complex disease driven by abnormal genetic, and epigenetic alterations, as well as environmental factors. Epigenetic changes resulting in aberrant gene expression are dynamic and modifiable features of many cancer types. A significant ...

Recently it has been proposed that di-methylation of histone H3 on lysine 4 (H3K4me2) acts as an epigenetic memory to maintain transcriptional patterns in developing tissues. This model suggests that there may be a requirement to reprogram this modification in the germline to prevent transcriptional memory from being inappropriately transmitted to the next ...

During development, epigenetic programs are "installed" on the genome that direct differentiation and normal tissue and organ function in adulthood. Consequently, development is also a period of susceptibility to reprogramming of the epigenome. Developmental reprogramming occurs when an adverse stimulus or insult interrupts the proper ...

BackgroundMale-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive ...

Abstract The mechanisms of nuclear reprogramming following somatic cell nuclear transfer (SCNT) to enucleated oocytes or factor-based reprogramming are poorly understood. In this study global transcriptional analysis was performed on a number of different rhesus monkey (Macaca mulatta) cell and tissue samples, including rhesus-induced pluripotent stem ...

DNA methylation is an important epigenetic mechanism, affecting normal development and playing a key role in reprogramming epigenomes during stem cell derivation. Here we report on DNA methylation patterns in native monkey embryonic stem cells (ESCs), fibroblasts, and ESCs generated through somatic cell nuclear transfer (SCNT), identifying and comparing ...

Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is ...

Epigenetic reprogramming implies changes in germ and somatic cells of an embryo, which are the consequences of gene activity regulation by means of DNA methylation, histone modification, and altered chromatin compaction. This suggests that epigenetic changes in mammalian cell nucleus occur during gametogenesis and toti-potent zygote ...

Increasing evidence suggests that epigenetic regulation is key to the maintenance of the stem cell state. Chromatin is the physiological form of eukaryotic genomes and the substrate for epigenetic marking, including DNA methylation, post-translational modifications of histones and the exchange of core histones with histone variants. The chromatin template ...

Plants and animals reproduce sexually via specialized, highly differentiated gametes. Yet, gamete formation drastically differs between the two kingdoms. In flowering plants, the specification of cells destined to enter meiosis occurs late in development, gametic and accessory cells are usually derived from the same meiotic product, and two distinct female gametes involved in double fertilization ...

Epithelial-to-mesenchymal transition (EMT) is an extreme example of cell plasticity that is important for normal development, injury repair and malignant progression. Widespread epigenetic reprogramming occurs during stem cell differentiation and malignant transformation, but EMT-related epigenetic reprogramming is ...

... et al. 2003; Smith et al. 2005). Various developmental abnormalities apparently arise from these epigenetic NT reprogramming errors, ... differences that predispose NT embryos to placentation failure, dev...

Induced pluripotent stem (iPS) cell reprogramming is a gradual epigenetic process that reactivates the pluripotent transcriptional network by erasing and establishing repressive epigenetic marks. In contrast to loci-specific epigenetic changes, heterochromatin domains undergo epigenetic ...

BackgroundEpigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next generation. In ...

It is now clear that aberrant DNA methylation observed in cancer cells is not restricted to a few CpG islands, but affects multiple loci. When this epigenetic event occurs at the 5-end of the regulatory region of genes, it is frequently associated with tr...

It is confident that mammalian somatic cell and embryonic stem cell can form whole individuals if they are transferred to enucleated oocytes at M phase. However, a large proportion of clones were stillborn or died within several months due to various reasons. Morphological abnormalities have also been observed in clones. The exact reasons for such abnormalities are not clear, but genetic or ...

While leukemia-originating stem cells are critical in the initiation and maintenance of leukemias, the existence of similar cell populations that may generate B-cell lymphoma upon mutation remains uncertain. Here we propose that committed lymphoid progenitor/precursor cells with an active V-D-J recombination program are the initiating cells of follicular lymphoma and mantle cell lymphoma when ...

Animal cloning through somatic cell nuclear transfer (NT) is very inefficient, probably due to insufficient reprogramming of the donor nuclei, which in turn would cause the dysregulation of gene expression. X-Chromosome inactivation (XCI) is a multi-step epigenetic process utilized by mammals to achieve dosage compensation in females. Our aim was to ...

Somatic cells have been reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors, such as Oct3/4, Sox2, Klf4 and c-Myc. Induced pluripotent stem (iPS) cells from a patient's somatic cells could be a useful source for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as ...

Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming is a continuous stochastic process where almost ...

It is widely accepted that cancer results from an array of epigenetic and genetic alterations, particularly aberrant epigenetic patterns that are a hallmark of every cancer type studied. Another well-known feature of cancer cells is the array of abnormalities in their nuclear structure. Although it is known that nuclear structure has ...

Epigenetic is the study of heritable changes in gene expression that occur without changes in DNA sequence. This process is important for gene expression and genome stability and its disruption is now thought to play a key role in the onset and progression of numerous tumor types. The most studied epigenetic phenomena includes post-translational ...

An important step during plant development is the transition from juvenile to adult growth. It is only after this transition that plants are reproductively competent. Given the great danger that transposon activity represents to the germ line, this may also be an important period during development with respect to transposon regulation and silencing. We demonstrate that a change in expression of a ...

Multipotent stem cells have the potential to establish a new field of promising regenerative medicine to treat tissue damage, genetic disorders, and degenerative diseases. However, limited resource of stem cells has turned to be an evitable obstacle in clinical applications. We utilized a simple in vitro epigenetic reprogramming approach to convert skin ...

Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem ...

Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem ...

Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, ...

Embryos derived by somatic cell nuclear transfer (SCNT) produce few pregnancies that result in a live, healthy offspring. This has largely been attributed to the aberrant reprogramming of the somatic cell DNA used for cloning. In order to improve the efficiency of cloning there is a great deal of research needed to determine the role of proteins involved ...

Context: Increased epigenetic variability in the placenta may have evolved in response to its role in mediating the conflicting demands of the mother and fetus. One essential guardian of early pregnancy maintenance is the placental hormone human chorionic gonadotropin (HCG).Objective: Among the four primate-specific duplicate HCG?-coding genes, chorionic gonadotropin-?8 (CGB8) ...

Genomic imprinting, an epigenetic gene-marking phenomenon that occurs in the germline, leads to parental-origin-specific expression of a small subset of genes in mammals. Imprinting has a great impact on normal mammalian development, fetal growth, metabolism and adult behavior. The epigenetic imprints regarding the parental origin are established during ...

Epigenetic modifications characterized by DNA methylation, histone modifications, and chromatin remodeling are important regulators in a number of biological processes, including spermatogenesis. Several genes in the testes are regulated through epigenetic mechanisms, indicating a direct influence of epigenetic mechanisms on the ...

Ethanol is a classic teratogen capable of inducing a wide range of developmental abnormalities. Studies in animal models suggest that differences in timing and dosage underlie this variability, with three particularly important developmental periods: preconception, preimplantation, and gastrulation. These periods of teratogenesis correlate with peak periods of epigenetic ...

Studies carried out in cultured cells have implicated modifiers of epigenetic reprogramming in the regulation of telomere length, reporting elongation in cells that were null for DNA methyltransferase DNA methyltransferase 1 (Dnmt1), both de novo DNA methyltransferases, Dnmt3a and Dnmt3b or various histone methyltransferases. To investigate this further, ...

Ever since the derivation of the first human embryonic stem cell line, hopes have persisted for the treatment of a wide range of cellular degenerative diseases. However, significant immuno-incompatibility between donor cells and recipient patients remains an unsolved challenge. Currently, three main strategies are investigated in humans to create autologous pluripotent stem cells: somatic cell ...

Placental deficiencies are linked with developmental abnormalities in cattle produced by somatic cell nuclear transfer (SCNT). To investigate whether the aberrant expression of imprinted genes in placenta was responsible for fetal overgrowth and placental hypertrophy, quantitative expression analysis of six imprinted genes (H19, XIST, IGF2R, SNRPN, PEG3, and IGF2) was ...

The advent of induced pluripotent stem cells (iPSCs) has brought the goal of using patient-derived cells for tissue repair closer to reality. However, the mechanisms involved in reprogramming to a pluripotent state are still not clear. It is understood that reprogramming to pluripotency involves epigenetic remodeling and the ...

In mammalian cloning, evidence suggests that genomic reprogramming factors are located in the nucleus rather than the cytoplasm of oocytes or zygotes. However, little is known about the mechanisms of reprogramming, and new methods using nuclear factors have not succeeded in producing cloned mice from differentiated somatic cell nuclei. We aimed to ...

It is generally accepted that genetic predisposition plays a role in COPD development in susceptible individuals. Therefore, many candidate genes that could be linked to the development of disease have been examined in COPD. However, inconsistent results in different study populations often limit this approach, suggesting that not only genetics, but also other factors, may be contributed to the ...

The mammalian totipotent and pluripotent lineage exhibits genome-wide dynamics with respect to DNA methylation content. The first phase of global DNA demethylation and de novo remethylation occurs during preimplantation development and gastrulation, respectively, while the second phase occurs in primordial germ cells and primary oocytes/prospermatogonia, respectively. These dynamics are indicative ...

Alternanthera philoxeroides (alligator weed) is an invasive weed that can colonize both aquatic and terrestrial habitats. Individuals growing in different habitats exhibit extensive phenotypic variation but little genetic differentiation in its introduced range. The mechanisms underpinning the wide range of phenotypic variation and rapid adaptation to novel and changing environments remain ...

Over the past decade, it has become increasingly obvious that epigenetic mechanisms are an integral part of a multitude of brain functions that range from the development of the nervous system over basic neuronal functions to higher order cognitive processes. At the same time, a substantial body of evidence has surfaced indicating that several neurodevelopmental, ...

Epigenetic changes in tumours are associated not only with cancer development and progression, but also with resistance to chemotherapy. Aberrant DNA methylation at CpG islands and associated epigenetic silencing are observed during the acquisition of drug resistance. However, it remains unclear whether all of the observed changes are ...

Epigenetic mechanisms such as DNA methylation and histone modifications drive stable, clonally propagated changes in genes expression and can therefore serve as molecular mediators of pathway dysfunction in neoplasia. MDS is characterized by frequent epigenetic abnormalities, including the hypermethylation of genes that control proliferation, adhesion, and ...

A decade after cloning the sheep Dolly, the induction of pluripotency by transcription factors has further revolutionized the possibilities of reprogramming a cell's identity, with exciting prospects for personalized medicine. Establishing totipotency during natural reproduction remains, however, exceedingly more efficient than in reproductive cloning or in transcription ...

We recently demonstrated that somatic cells from adult primates could be reprogrammed into a pluripotent state by somatic cell nuclear transfer. However, the low efficiency with donor cells from one monkey necessitated the need for large oocyte numbers. Here, we demonstrate nearly threefold higher blastocyst development and embryonic stem (ES) cell derivation rates with ...

Bovine preimplantation embryos derived from nuclear transfer experiments exhibit a global state of genomic hypermethylation that likely account for the large number of developmental abnormalities observed to date. The central hypotheses of this work is that the genomic hypermethylation and improper epigenetic reprogramming reported in studies of bovine ...

Paramutation describes the transfer of an acquired epigenetic state to an unlinked homologous locus, resulting in a meiotically heritable alteration in gene expression. Early investigations of paramutation characterized a mode of change and inheritance distinct from mendelian genetics, catalyzing the concept of the epigenome. Numerous examples of paramutation and ...

Although the critical role for epigenetic mechanisms in development and cell differentiation has long been appreciated, recent evidence reveals that these mechanisms are also employed in postmitotic neurons as a means of consolidating and stabilizing cognitive-behavioral memories. In this review, we discuss evidence for an "epigenetic code" in the central ...

Despite the involvement of genetic alterations in neoplastic cell transformation, it is increasingly evident that abnormal epigenetic patterns, such as those affecting DNA methylation and histone posttranslational modifications (PTMs), play an essential role in the early stages of tumor development. This finding, together with the evidence that epigenetic ...

Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA repair. An ...

Endometriosis, a common, benign, estrogen-dependent disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue that is found primarily in the peritoneum, ovaries and rectovaginal septum. Recently, endometriosis has been alternatively described as an immune disease, a genetic disease and a disease caused by exposure to environmental factors, ...

BackgroundSuccessful reprogramming of a somatic genome to produce a healthy clone by somatic cells nuclear transfer (SCNT) is a rare event and the mechanisms involved in this process are poorly defined. When serial or successive rounds of cloning are performed, blastocyst and full term development rates decline even further with the increasing rounds of cloning. Identifying ...

Heterochromatin at pericentric satellites, characterized by a specific chromatin signature and chromocenter organization, is of paramount importance for genome function. Re-establishment of this organization after fertilization takes place in the context of genome-wide epigenetic reprogramming. We review how the asymmetry in histone variants and ...

With relatively low efficiency, differentiated cells can be reprogrammed to a pluripotent state by ectopic expression of a few transcription factors. An understanding of the mechanisms that underlie data emerging from such experiments can help design optimal strategies for creating pluripotent cells for patient-specific regenerative medicine. We have developed a computational ...

Nuclear reprogramming is critical for animal cloning and stem cell creation through nuclear transfer, which requires extensive remodeling of chromosomal architecture involving dramatic changes in chromatin-binding proteins. To understand the mechanism of nuclear reprogramming, it is critical to identify chromatin-binding factors specify the ...

The generation of induced pluripotent stem cells (iPSCs) from somatic cells demonstrated that adult mammalian cells can be reprogrammed to a pluripotent state by the enforced expression of a few embryonic transcription factors. This discovery has raised fundamental questions about the mechanisms by which transcription factors influence the epigenetic ...

During embryogenesis a timely and coordinated expression of different subsets of genes drives the formation of skeletal muscles in response to developmental cues. In this review, we will summarize the most recent advances on the �epigenetic network� that promotes the transcription of selective groups of genes in muscle progenitors, through the concerted action of ...

Cancer is a pathology that is associated with aberrant gene expression and an altered metabolism. While changes in gene expression have historically been attributed to mutations, it has become apparent that epigenetic processes also play a critical role in controlling gene expression during carcinogenesis. Global changes in epigenetic ...

This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. ...

This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. ...

We report here that butyrate, a naturally occurring fatty acid commonly used as a nutritional supplement and differentiation agent, greatly enhances the efficiency of induced pluripotent stem (iPS) cell derivation from human adult or fetal fibroblasts. After transient butyrate treatment, the iPS cell derivation efficiency is enhanced by 15- to 51-fold using either retroviral or piggyBac transposon ...

Human reproductive cloning is a much disputed ethical issue. This technology is often condemned as being contrary to human dignity. However, there are also risk arguments. An ethical argument that is often put forward by scientists but seldom developed in more detail focuses on health risks in animal cloning. There is a high risk that animal clones exhibit abnormalities and these are increasingly ...

For the successful production of cloned animals by somatic cell nuclear transfer (NT), the epigenetic status of the differentiated donor cell is reversed to an embryonic totipotent status. However, in NT embryos, this process is aberrant, with genomic hypermethylation consistently observed. Here, we investigated the effects of silencing DNA ...

Epigenetic mechanisms maintain heritable changes in gene expression and chromatin organization over many cell generations. Importantly, deregulated epigenetic mechanisms play a key role in a wide range of human malignancies, including liver cancer. Hepatocellular carcinoma (HCC), which originates from the hepatocytes, is by far the most common liver ...

Epigenetic mechanisms are thought to help regulate the unique transcription program that is established in germ cell development. During the germline cycle of many organisms, the epigenome undergoes waves of extensive resetting events, while a part of epigenetic modification remains faithful to specific loci. Little is known about the mechanisms underlying ...

The overall objective of this research was to identify genes that are aberrantly methylated in epithelial ovarian cancer. Our approach was to treat or mock treat primary normal or tumor cultured cells with drugs that inhibit DNA methyltransferase activity...

Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear. Here we report that, within mouse zygotes, ...

and after meiosis. Hypomethyla- tion in mice is associated with chromosome aneuploidy12,34. Although most aneuploidies are embryonic lethal and would not be detectable in adult offspring, abnormal num- bers of sex that spontaneous sex chromosome aneuploidy occurs more frequently in offspring from Dnmt3l haploinsufficient sires

Epigenetic reprogramming has a crucial role in establishing nuclear totipotency in normal development and in cloned animals. Insulin-like growth factor-2 receptor (Igf-2r) is a tissue-specifically and species-dependently imprinted gene, regulated by epigenetic modifications. The diversity of Igf-2r imprinting suggests that the success ...

In this issue of Cell Stem Cell, Ku et�al. (2010) demonstrate that iPSCS derived from Friedreich's ataxia patients exhibit expansion of the causative (GAA)(n) repeat, consistent with the repeat instability observed during intergenerational transmissions in humans. Furthermore, the epigenetic signature of the disease remains intact in Friedreich's ataxia iPSCs. PMID:21040891

Global demethylation is required for early zygote development to establish stem cell pluripotency, yet our findings reiterate this epigenetic reprogramming event in somatic cells through ectopic introduction of mir-302 function. Here, we report that induced mir-302 expression beyond 1.3-fold of the concentration in human embryonic stem (hES) H1 and H9 ...

Global demethylation is required for early zygote development to establish stem cell pluripotency, yet our findings reiterate this epigenetic reprogramming event in somatic cells through ectopic introduction of mir-302 function. Here, we report that induced mir-302 expression beyond 1.3-fold of the concentration in human embryonic stem (hES) H1 and H9 ...

Analyses of molecular events associated with reprogramming somatic nuclei to pluripotency are scarce. We previously reported the reprogramming of epithelial cells by extract of undifferentiated embryonal carcinoma (EC) cells. We now demonstrate reprogramming of DNA methylation and histone modifications on regulatory regions of the ...

Integrity of the germline genome is essential for the production of viable gametes and successful reproduction. In mammals, the generation of gametes involves extensive epigenetic changes (DNA methylation and histone modification) in conjunction with changes in chromosome structure to ensure flawless progression through meiotic recombination and packaging of the genome into ...

Acute systemic inflammation from infectious and noninfectious etiologies has stereotypic features that progress through an initiation (proinflammatory) phase, an adaptive (anti-inflammatory) phase, and a resolution (restoration of homeostasis) phase. These phase-shifts are accompanied by profound and predictable changes in gene expression and metabolism. Here, we review the emerging concept that ...

Fertilization of the oocyte by the sperm results in the formation of a totipotent zygote, in which the maternal and paternal chromatin is enclosed in two pronuclei undergoing distinct programmes of transcriptional activation and chromatin remodelling. The highly packaged paternal chromatin delivered by the sperm is decondensed and acquires a number of specific epigenetic ...

DNA methylation is a stable and heritable epigenetic mark, and it is one of the best characterized epigenetic modifications. Active DNA demethylation has been reported both in plant and animal cells, and the mechanism behind it is becoming clear in plant. Whereas a bona fide enzyme, which is responsible for active DNA demethylation, have not been ...

Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more ...

One of the key questions in the study of mammalian gene regulation is how epigenetic methylation patterns on histones and DNA are initiated and established. These stable, heritable, covalent modifications are largely associated with the repression or silencing of gene transcription, and when deregulated can be involved in the development of human diseases such as cancer. This ...

Acute leukemias are characterized by recurring chromosomal aberrations and gene mutations which are critical to disease pathogenesis. It is now evident that epigenetic modifications including DNA methylation and histone modifications contribute significantly to the leukemogenic phenotype. An additional layer of epigenetic complexity is ...

BackgroundAberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy ...

The mammalian oocyte possesses powerful reprogramming factors, which can reprogram terminally differentiated germ cells (sperm) or somatic cells within a few cell cycles. Although it has been suggested that use of oocyte-derived transcripts may enhance the generation of induced pluripotent stem cells, the reprogramming factors in ...

The epigenomes of early mammalian embryos are extensively reprogrammed to acquire a totipotent developmental potential. A major initial event in this reprogramming is the active loss/demethylation of 5-methylcytosine (5mC) in the zygote. Here, we report on findings that link this active demethylation to molecular mechanisms. We detect ...

The dynamics of genome modification that occurred from the initial hybridization event to the stabilization of allopolyploid species remains largely unexplored. Here, we studied inheritance and expression of rDNA loci in the initial generations of Brassica napus allotetraploids (2n?=?38, AACC) resynthesized from Brassica oleracea (2n?=?18, CC) and B. rapa (2n?=?20, AA) and compared the patterns to ...

Tissue repair is a complex process that requires wound-edge cells to proliferate and migrate, which in turn necessitates induction of a large repair transcriptome. Epigenetic modifications have emerged as crucial regulators of gene expression. Here, we ask whether epigenetic reprogramming might contribute to the concerted induction of ...

CpG island methylation is an epigenetic modification of DNA associated with the silencing of gene transcription. The hypothesis of this proposal is that breast cancers develop along different pathways, some involving aberrant CpG island methylation for ge...

CpG island methylation is an epigenetic modification of DNA associated with the silencing of gene transcription. The hypothesis of this proposal is that breast cancers develop along different pathways, some involving aberrant CpG island methylation for ge...

Epigenetic genome modifications such as DNA methylation appear to be involved in various diseases. Here, we suggest that the levels of DNA methylation at the BssHII methylation-sensitive restriction enzyme sites in the human REELIN (RELN) gene in the forebrain vary among individuals. Interestingly, although a statistically significant correlation between the levels of DNA ...

Genomic imprinting refers to an epigenetic mark that distinguishes parental alleles and results in a monoallelic, parental-specific expression pattern in mammals. Few phenomena in nature depend more on epigenetic mechanisms while at the same time evading them. The alleles of imprinted genes are marked epigenetically at discrete ...

This volume is an outgrowth of a symposium entitled "Epigenetics and Neuropsychiatric Diseases: Mechanisms Mediating Nature and Nurture" presented at the 88th Annual Conference of the Association for Nervous and Mental Diseases, held on December 5, 2008 at the New York Academy of Medicine. Dolores Malaspina (New York University Medical Center) and Mark F. Mehler (Albert ...

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells ...

Following hybridization with embryonic stem (ES) cells, somatic genomes are epigenetically reprogrammed and acquire pluripotency. This results in the transcription of somatic genome-derived tissue-specific genes upon differentiation. During nuclear reprogramming, it is expected that DNA and chromatin modifications, believed to function ...

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development ...

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development ...

Although epidemiological studies support the role of environment in a wide range of human cancers, the precise mechanisms by which environmental exposures promote cancer development and progression remain poorly understood. Environmental factors have been proposed to promote the development of malignancies by eliciting epigenetic changes; however, it is only with recent ...

Malignant Melanoma remains one of the most deadly human cancers with no effective cures for metastatic disease. The poor efficacy of current therapy in advanced melanoma highlights the need for better understanding of molecular mechanisms contributing to the disease. Recent work has shown that epigenetic changes, including aberrant DNA methylation, lead to ...

Tumour cells are characterized by karyotype instability, which is accompanied by specific events in the chromatin structure and epigenetic patterns. Epigenetics involves heritable changes in the physical and biochemical state of chromatin, which have no effect on DNA sequences; therefore, changes in the nuclear radial arrangement of chromosomes can also be ...

Regenerative medicine using pluripotent/multipotent stem cells holds a great promise in developing therapies for treating developmental abnormalities, degenerative disorders and aging-related illness. However, supply and safety of the stem cells are two major problems with today's regenerative medicine. Recent development of induced pluripotent stem cells (iPS cells or iPSCs) has overcome the ...

In addition to genetic events, a variety of epigenetic events have been widely reported to contribute to the onset of many diseases including cancer. DNA methylation and histone modifications (such as acetylation, methylation, sumoylation, and phosphorylation) involving chromatin remodelling are among the most studied epigenetic mechanisms for regulation ...

BackgroundPreviously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT.ResultsGenome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA ...

Phenotypic diversity is shaped by both genetic and epigenetic mechanisms that program tissue specific patterns of gene expression. Cells, including neurons, undergo massive epigenetic reprogramming during development through modifications to chromatin structure, and by covalent modifications of the DNA through methylation. There is ...

The epigenetic regulation of the floral repressor Flowering Locus C (FLC) is one of the critical factors that determine flowering time in Arabidopsis thaliana. Although many FLC regulators, and their effects on FLC chromatin, have been extensively studied, the epigenetic resetting of FLC has not yet been thoroughly characterized. Here, we investigate the ...

BackgroundThe interaction between the karyoplast and cytoplast plays an important role in the efficiency of somatic cell nuclear transfer (SCNT), but the underlying mechanism remains unclear. It is generally accepted that in nuclear transfer embryos, the reprogramming of gene expression is induced by epigenetic mechanisms and does not involve modifications ...

Kevin Eggan received his PhD in Biology from the Massachusetts Institute of Technology in February 2003. He is currently an Assistant Professor of Stem Cell and Regenerative Biology at Harvard University. Dr Eggan has devoted the last 7 years to performing stem cell research. He is currently leading a research group that is investigating the mechanisms regulating epigenetic ...

The possibility of regenerating whole plants from somatic differentiated cells emphasizes the plasticity of plant development. Cell-type respecification during regeneration can be induced in adult tissues as a consequence of injuries, changes in external or internal stimuli or changes in positional information. However, in many plant species, switching the developmental program of adult cells ...

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 ...

Induced pluripotent stem (iPS) cells have been generated from a variety of somatic cell types via introduction of transcription factors that mediate pluripotency. However, it is unknown that all cell types can be reprogrammed and whether the origin of the parental cell ultimately determines the behavior of the resultant iPS cell line. We sought to determine whether human ...

PURPOSE: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). CONCLUSION: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, ...

Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, ...

An increasing body of evidence suggests that cancer cells acquire "stem-like" epigenetic and signaling characteristics during the tumorigenic process, including global DNA hypo-methylation, gene-specific DNA hyper-methylation, and small RNA deregulation. RNAs have been known to be epigenetic regulators, both in stem cells and in differentiated cells. A ...

For every cell, there is a time to live and a time to die. It is apparent that cell life and death decisions are taken by individual cells based on their interpretation of physiological or non-physiological stimuli, or their own self-assessment of internal damage or changes in their environment. Apoptosis or programmed cell death is a key regulator of physiological growth control and regulation of ...

Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic ...

Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer ...

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, ...

Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in�germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory ...

The transplantation of somatic cell nuclei to enucleated eggs has shown that genes can be reprogrammed to an embryonic pattern of expression, thereby indicating a reversal of their epigenetic state. However, in Xenopus nuclear transfer experiments using both endoderm and neuroectoderm donor cells, we have observed substantial overexpression of donor cell ...

Xenotransplantation is a rapidly expanding field of research and cloned miniature pigs have been considered as a model animal for it. However, the efficiency of somatic cell nuclear transfer (SCNT) is extremely low, with most clones resulting in early lethality and several kinds of aberrant development. A possible explanation for the developmental failure of SCNT embryos is ...

Cloning mammals has been successful for many years by splitting an early embryo or transferring embryonic cell nuclei into enucleated oocytes. Cloning is now possible with adult somatic cells. At present, cloning efficiency--as determined by the proportion of live offspring developed from all oocytes that received donor cell nuclei--is low regardless of the cell type (including, embryonic stem ...

The events regulating human preimplantation development are still largely unknown owing to a scarcity of material, ethical and legal limitations and a lack of reliable techniques to faithfully amplify the transcriptome of a single cell. Nonetheless, human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic ...

Neural stem cells (NSCs) lose their competency to generate region-specific neuronal populations at an early stage during embryonic brain development. Here we investigated whether epigenetic modifications can reverse the regional restriction of mouse adult brain subventricular zone (SVZ) NSCs. Using a variety of chemicals that interfere with DNA methylation and histone ...

Neural stem cells (NSCs) lose their competency to generate region-specific neuronal populations at an early stage during embryonic brain development. Here we investigated whether epigenetic modifications can reverse the regional restriction of mouse adult brain subventricular zone (SVZ) NSCs. Using a variety of chemicals that interfere with DNA methylation and histone ...

Nuclear importing system and nuclear factors play important roles in mediating nuclear reprogramming and zygotic gene activation. However, the components and mechanisms that mediate nuclearly specific targeting of the nuclear proteins during nuclear reprogramming and zygotic gene activation remain largely unknown. Here, we identified a novel member of the ...

It is now over a decade since the birth, in 1996, of Dolly the first animal to be produced by nuclear transfer using an adult derived somatic cell as nuclear donor. Since this time similar techniques have been successfully applied to a range of species producing live offspring and allowing the development of transgenic technologies for agricultural, biotechnological and medical uses. However, ...

Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, therefore, the nuclear transfer (NT) method has been thought ...

Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a ...

This critical care perspective appraises reprogramming of gene expression in inflammatory diseases as an emerging concept of clinical importance. We emphasize gene reprogramming that "silences" acute proinflammatory genes during severe systemic inflammation, wherein in the systemic inflammatory response syndrome (SIRS) exists as a continuum during severe ...

Using single transcription factors to reprogram cells could produce important insights into the epigenetic mechanisms that direct normal differentiation, or counter inappropriate plasticity, or even provide new ways of manipulating normal ontogeny in vitro to control lineage diversification and differentiation. We enforced Pdx1 expression from the ...

Epigenetics is defined as "the study of mitotically and/or meiotically heritable changes in gene expression that cannot be explained by changes in the DNA sequence". Setting up the epigenetic program is crucial for correct development and its stable inheritance throughout its lifespan is essential for the maintenance of the tissue- and cell-specific ...