Abstract
Epigenetic mechanisms modulate genome function by writing, reading and erasing chromatin structural features. These have an impact on gene expression, contributing to the establishment, maintenance and dynamic changes in cellular properties in normal and abnormal situations. Great effort has recently been undertaken to catalogue the genome-wide patterns of epigenetic marks—creating reference epigenomes—which will deepen our understanding of their contributions to genome regulation and function with the promise of revealing further insights into disease etiology. The foundation for these global studies is the smaller scale experimentally-derived observations and questions that have arisen through the study of epigenetic mechanisms in model systems. One such system is genomic imprinting, a process causing the mono-allelic expression of genes in a parental-origin specific manner controlled by a hierarchy of epigenetic events that have taught us much about the dynamic interplay between key regulators of epigenetic control. Here, we summarize some of the most noteworthy lessons that studies on imprinting have revealed about epigenetic control on a wider scale. Specifically, we will consider what these studies have revealed about: the variety of relationships between DNA methylation and transcriptional control; the regulation of important protein-DNA interactions by DNA methylation; the interplay between DNA methylation and histone modifications; and the regulation and functions of long non-coding RNAs.
Highlights
Epigenetic mechanisms modulate genome function by writing, reading and erasing chromatin structural features
Cells are subject to dynamic changes in gene expression, dependent, for example, on intrinsic and extrinsic cues, which can be mediated through epigenetic processes
Reintroduction of REST into the REST/ cells reverted the methylation status of the low methylated regions (LMRs) to the normal low levels [43]. These findings suggest DNA methylation may not have a direct role in silencing gene expression in all situations
Summary
Genomic imprinting is a process causing the mono-allelic expression of a specific subset of mammalian genes in a parental origin specific manner (reviewed in [8,9])—i.e., genes that are expressed either from the paternally inherited chromosome or from the maternally inherited chromosome (paternal allele and maternal allele ) are imprinted. The mechanisms through which ICRs control gene expression in their respective clusters are diverse and remain the subject of active research, including analysis of regulation by ncRNAs and of the relationships between DNA methylation and histone and non-histone proteins. Both in imprinted and non-imprinted contexts, little is known about why certain DNA sequences become methylated and not others, or how this may change dynamically within a sequence such as a particular CpG island at a gene promoter. ZFP57 binds methylated DNA and is thought to recruit methyltransferases to imprinting control regions preventing them from loss of their imprints
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