Sanli Ildem, Feil Robert
Institute of Molecular Genetics (IGMM), UMR-5535, CNRS, University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.
Institute of Molecular Genetics (IGMM), UMR-5535, CNRS, University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.
Int J Biochem Cell Biol. 2015 Oct;67:139-47. doi: 10.1016/j.biocel.2015.04.004. Epub 2015 Apr 20.
Hundreds of protein-coding genes and regulatory non-coding RNAs (ncRNAs) are subject to genomic imprinting. The mono-allelic DNA methylation marks that control imprinted gene expression are somatically maintained throughout development, and this process is linked to specific chromatin features. Yet, at many imprinted genes, the mono-allelic expression is lineage or tissue-specific. Recent studies provide mechanistic insights into the developmentally-restricted action of the 'imprinting control regions' (ICRs). At several imprinted domains, the ICR expresses a long ncRNA that mediates chromatin repression in cis (and probably in trans as well). ICRs at other imprinted domains mediate higher-order chromatin structuration that enhances, or prevents, transcription of close-by genes. Here, we present how chromatin and ncRNAs contribute to developmental control of imprinted gene expression and discuss implications for disease. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.
数百个蛋白质编码基因和调控性非编码RNA（ncRNA）受到基因组印记的影响。控制印记基因表达的单等位基因DNA甲基化标记在整个发育过程中体细胞内保持稳定，并且这一过程与特定的染色质特征相关。然而，在许多印记基因中，单等位基因表达具有谱系或组织特异性。最近的研究为“印记控制区”（ICR）在发育受限的作用机制提供了见解。在几个印记结构域中，ICR表达一种长链ncRNA，其在顺式（可能也在反式）中介导染色质抑制。其他印记结构域的ICR介导高阶染色质结构形成，增强或阻止附近基因的转录。在这里，我们阐述染色质和ncRNA如何对印记基因表达的发育控制做出贡献，并讨论其对疾病的影响。本文是名为“发育和疾病中的表观遗传学动态”的定向专题的一部分。
