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A growing number of functions are emerging for RNA interference (RNAi) in the nucleus, in addition to well-characterized roles in post-transcriptional gene silencing in the cytoplasm. Epigenetic modifications directed by small RNAs have been shown to cause transcriptional repression in plants, fungi and animals. Additionally, increasing evidence indicates that RNAi regulates transcription through interaction with transcriptional machinery. Nuclear small RNAs include small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) and are implicated in nuclear processes such as transposon regulation, heterochromatin formation, developmental gene regulation and genome stability. [ABSTRACT FROM AUTHOR]

It is known that information that is not contained in the DNA sequence - epigenetic information - can be inherited from the parent to the offspring. However, many questions remain unanswered regarding the extent and mechanisms of such inheritance. In this Review, we consider the evidence for transgenerational epigenetic inheritance via the gametes, including cases of environmentally induced epigenetic changes. The molecular basis of this inheritance remains unclear, but recent evidence points towards diffusible factors, in particular RNA, rather than DNA methylation or chromatin. Interestingly, many cases of epigenetic inheritance seem to involve repeat sequences. [ABSTRACT FROM AUTHOR]

Enhancer function underlies regulatory processes by which cells establish patterns of gene expression. Recent results suggest that many enhancers are specified by particular chromatin marks in pluripotent cells, which may be modified later in development to alter patterns of gene expression and cell differentiation choices. These marks may contribute to the repertoire of epigenetic mechanisms responsible for cellular memory and determine the timing of transcription factor accessibility to the enhancer. Mechanistically, cohesin and non-coding RNAs are emerging as crucial players responsible for facilitating enhancer-promoter interactions at some genes. Surprisingly, these interactions may be required not only to facilitate initiation of transcription but also to activate the release of RNA polymerase II (RNAPII) from promoter-proximal pausing. [ABSTRACT FROM AUTHOR]

Induction of pluripotency by transcription factors has become a commonplace method to produce pluripotent stem cells. Great strides have been made in our understanding of the mechanism by which this occurs--particularly in terms of transcriptional and chromatin-based events--yet only a small part of the complete picture has been revealed. Understanding the mechanism of reprogramming to pluripotency will have important implications for improving the efficiency and quality of reprogramming and advancing therapeutic application of induced pluripotent stem cells. It will also help to reveal the machinery that stabilizes cell identity and to instruct the design of directed differentiation or lineage switching strategies. To inform the next phase in understanding reprogramming, we review the latest findings, highlight ongoing debates and outline future challenges. [ABSTRACT FROM AUTHOR]

Classically, quantitative geneticists have envisioned DNA sequence variants as the only source of heritable phenotypes. This view should be revised in light of accumulating evidence for widespread epigenetic variation in natural and experimental populations. Here we argue that it is timely to consider novel experimental strategies and analysis models to capture the potentially dynamic interplay between chromatin and DNA sequence factors in complex traits. [ABSTRACT FROM AUTHOR]

Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways — not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible in this organism, and emphasize the available tools. Screens exploit the well-studied behaviour of transposon systems, and the distinctive chromosomes allow an integration of cytogenetics into mutagenesis screens and analyses. The imminent completion of the maize genome sequence provides the essential resource to move seamlessly from gene to phenotype and back. [ABSTRACT FROM AUTHOR]

Assembly, mobilization and disassembly of nucleosomes can influence the regulation of gene expression and other processes that act on eukaryotic DNA. Distinct nucleosome-assembly pathways deposit dimeric subunits behind the replication fork or at sites of active processes that mobilize pre-existing nucleosomes. Replication-coupled nucleosome assembly appears to be the default process that maintains silent chromatin, counteracted by active processes that destabilize nucleosomes. Nucleosome stability is regulated by the combined effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent nucleosome remodellers, post-translational modifications and histone variants. Recent studies suggest that histone turnover helps to maintain continuous access to sequence-specific DNA-binding proteins that regulate epigenetic inheritance, providing a dynamic alternative to histone-marking models for the propagation of active chromatin. [ABSTRACT FROM AUTHOR]

An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modification in cancer cells on a gene-by-gene basis; among their results has been the seminal finding of transcriptional silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation. However, recent technological advances are now allowing cancer epigenetics to be studied genome-wide — an approach that has already begun to provide both biological insight and new avenues for translational research. It is time to 'upgrade' cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches. [ABSTRACT FROM AUTHOR]

Epidemiological evidence increasingly suggests that environmental exposures early in development have a role in susceptibility to disease in later life. In addition, some of these environmental effects seem to be passed on through subsequent generations. Epigenetic modifications provide a plausible link between the environment and alterations in gene expression that might lead to disease phenotypes. An increasing body of evidence from animal studies supports the role of environmental epigenetics in disease susceptibility. Furthermore, recent studies have demonstrated for the first time that heritable environmentally induced epigenetic modifications underlie reversible transgenerational alterations in phenotype. Methods are now becoming available to investigate the relevance of these phenomena to human disease. [ABSTRACT FROM AUTHOR]

Pluripotent stem cells, similar to more restricted stem cells, are able to both self-renew and generate differentiated progeny. Although this dual functionality has been much studied, the search for molecular signatures of 'stemness' and pluripotency is only now beginning to gather momentum. While the focus of much of this work has been on the transcriptional features of embryonic stem cells, recent studies have indicated the importance of unique epigenetic profiles that keep key developmental genes 'poised' in a repressed but activatable state. Determining how these epigenetic features relate to the transcriptional signatures of ES cells, and whether they are also important in other types of stem cell, is a key challenge for the future. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that chromatin modifications are important regulators of mammalian telomeres. Telomeres provide well studied paradigms of heterochromatin formation in yeast and flies, and recent studies have shown that mammalian telomeres and subtelomeric regions are also enriched in epigenetic marks that are characteristic of heterochromatin. Furthermore, the abrogation of master epigenetic regulators, such as histone methyltransferases and DNA methyltransferases, correlates with loss of telomere-length control, and telomere shortening to a critical length affects the epigenetic status of telomeres and subtelomeres. These links between epigenetic status and telomere-length regulation provide important new avenues for understanding processes such as cancer development and ageing, which are characterized by telomere-length defects. [ABSTRACT FROM AUTHOR]

Overlapping epigenetic mechanisms have evolved in eukaryotic cells to silence the expression and mobility of transposable elements (TEs). Owing to their ability to recruit the silencing machinery, TEs have served as building blocks for epigenetic phenomena, both at the level of single genes and across larger chromosomal regions. Important progress has been made recently in understanding these silencing mechanisms. In addition, new insights have been gained into how this silencing has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome. [ABSTRACT FROM AUTHOR]

The developmental programme of embryogenesis is controlled by both genetic and epigenetic mechanisms. An emerging theme from recent studies is that the regulation of higher-order chromatin structures by DNA methylation and histone modification is crucial for genome reprogramming during early embryogenesis and gametogenesis, and for tissue-specific gene expression and global gene silencing. Disruptions to chromatin modification can lead to the dysregulation of developmental processes, such as X-chromosome inactivation and genomic imprinting, and to various diseases. Understanding the process of epigenetic reprogramming in development is important for studies of cloning and the clinical application of stem-cell therapy. [ABSTRACT FROM AUTHOR]

Patterns of DNA methylation and chromatin structure are profoundly altered in neoplasia and include genome-wide losses of, and regional gains in, DNA methylation. The recent explosion in our knowledge of how chromatin organization modulates gene transcription has further highlighted the importance of epigenetic mechanisms in the initiation and progression of human cancer. These epigenetic changes ? in particular, aberrant promoter hypermethylation that is associated with inappropriate gene silencing ? affect virtually every step in tumour progression. In this review, we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer. [ABSTRACT FROM AUTHOR]

Site-specific initiation of DNA replication is a conserved function in all organisms. In Escherichia coli and Saccharomyces cerevisiae, DNA replication origins are sequence specific, but in multicellular organisms, origins are not so clearly defined. In this article, I present a model of origin specification by epigenetic mechanisms that allows the establishment of stable chromatin domains, which are characterized by autonomous replication. According to this model, origins of DNA replication help to establish domains of gene expression for the generation of cell diversity. [ABSTRACT FROM AUTHOR]

The article focuses on a research related to the impact of epigenetic silencing. It discusses that MicroRNAs regulate gene expression by gene coding leading to their fission in plants and animals. It suggest that miRNAs might epigenetically regulate stress-responsive genes.The physiological regulation of this epigenetic miRNA-induced silencing pathway.

The article discusses the research done on RNA interference (RNAi). It references the studies by F. K. Teixeira and colleagues, published in the January 29, 2009 issue of "Science," and R. K. Slotkin and colleagues, published in the previous issue of " Cell." Teixeira and colleagues found that RNAi improves DNA methylation patterns in the succeeding generations. Furthermore, the study of R. K. Slotkin and colleagues found that RNAi has a defensive role in normal pollen development.

The article focuses on the role of epigenetics in gene expression. It states that recent studies which utilize yeast as their subject revealed that divergence in nucleosome positioning, which also causes variability in gene expression, can now be encoded in the genome. An overview of the studies conducted regarding variable occupancy and sequence changes altering nucleosome positioning are also offered.

The article reexamines a research paper entitled "Modifiers of Epigenetic Reprogramming Show Paternal Effects in the Mouse," by S. Chong and colleagues. In this study, the authors used the mouse agouti viable yellow allele as a reporter for alterations in the inheritance of an epigenetic state. Their study revealed an important implication of such trans-generational epigenetic inheritance.

The article discusses nucleotide excision repair (NER) after UV damage in which new histones are incorporated at the damage site instead of recycled histones. This finding raises many questions about the maintenance of epigenetic marks in the face of DNA damage. The article also discusses an assay developed by Almouzni and colleagues developed for the incorporation of histone variant H3.1 at sites of UV damage.

Discusses research being done on epigenetics. Reference to a study by J. Mager et al, published in a 2003 issue of 'Nature Genetics'; Information on X chromosome inactivation.

A letter to the editor is presented in response to the article "The genetics of inbreeding depression," by D. Charlesworth and J. H. Willis, in the 2009 issue.

The article discusses the impact of reprogramming on genomic and epigenomic integrity for the use of induced pluripotent stem cells (iPSC) in regenerative medicine and disease research. It states that researchers performed exome sequencing on 22 human iPSC lines and the fibroblast lines from which they derive to explore the use iPSCs in the applications. Additionally, another aspect of genomic integrity was studied by researchers using single-nucleotide polymorphism (SNP) arrays.

The article offers news briefs related to genetics. Role of epigenetic modification in providing a cellular memory of developmental or environmental effects early in life. MicroRNA evolution and the evolution of tissue identity are interconnected. study on the impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes.

The article discusses inbreeding effects in epigenesis. It mentions about the omic technology which enhances the knowledge of inbreeding effects. It discovers epigenetics to the differential regulation of gene expression, imprinting and gene silencing. Epigenetic differences among natural population is being linked with the variations of DNA methylation.

The article offers news briefs related to genetic research in 2009. A study offers an avenue on the use of engineered zinc finger nucleases in generating knockout rats. Another research also reveals heritable variation in epigenetic inheritance that contributes to the causality and heritability of complex diseases. Moreover, various organisms have different synonymous codons which play a significant role in the evolution.

The article offers information on the two antisense RNA transcripts, AIR and KCNQ1OT1. It mentions that the two antisense transcripts are normally expressed from paternally inherited chromosomes and are involved in silencing cis clusters of genes. It references two studies that show the effect of the antisense transcripts in gene-silencing and its direct, functional involvement in lineage-specific transcriptional repression, mediated via epigenetic modifications.

The article presents abstracts of various genetic research including "The fine-scale complex architecture of human copy-number variation," by G. Perry and colleagues, "High resolution mapping of epigenetic modifications of the rice genome uncovers interplay between DNA methylation,histone methylation and gene expression" by X. Li and colleagues and "Gene Expression dynamics in the macrophage exhibit criticality," by M. Nykter and colleagues.

The article evaluates a research paper entitled "Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island," by J. Lin and colleagues. The study demonstrates that for one promoter region cytosine methylation is accompanied by the presence of nucleosomes that are largely absent in this region in normal cells.

The article evaluates a research paper entitled "RNA-mediated epigenetic programming of a genome-rearrangement pathway," by M. Nowacki and colleagues. The study of unicellular eukaryote Oxytricha Trifallax adds to the understanding of how RNAs might transmit information across generations. It also demonstrates the intriguing possibility that RNA templates may be required in less widespread rearrangements in other eukaryotes, and suggests a role of RNAs in transgenerational effects.

The article evaluates a research entitled "Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription," by R. K. Ng and J. B. Gurdon. The study demonstrates that histone H3.3 is required for the persistence of some active gene states. Authors of the study conclude that the stable inheritance of cellular memory might provide an explanation for the decreasing success of nuclear transfer from more differentiated donor cell nuclei.

The article presents news briefs regarding genetic research. The genome of an Abyssian cat has been sequenced and annotated by comparing it with the genomes of other mammals. A genome-wide RNAi screen in cancer cells in humans has identified 28 epigenetic modifiers that transform a normal cell into a cancer cell. Two studies have determined an X-linked distorted gene in Drosophila simulans and the autosomal gene that has evolved to counter the action of the distorter.

The article provides information on a study by Rudolf Jaenisch and colleagues, which have demonstrated that global loss of imprinting leads to tumor formation. In the study, the researchers found that imprinting is an epigenetic tumor-suppressing phenomenon. When imprinting is lost, cells are immortalized through the inappropriate regulation of both tumor suppressors and oncogenes. Therefore for full transformation, genetic alterations are required.

Discusses a study which provided evidence for an epigenetic mechanism, with reference to a study by V. Sollars and colleagues published in the 2003 issue of 'Nature Genetics' journal. Effect of epigenetic alterations on phenotype fixation; Details of the experimental methods; Implications of the mechanism for evolutionary change.

Deals with several studies which provided evidence that assisted reproductive technology bring about epigenetic changes in the early embryo and lead to birth defects. Families with Beckwith-Wiedemann syndrome; Details of a case of Angelman syndrome following intracytoplasmic sperm injection.