Chromatin mechanisms in the developmental control of imprinted gene expression

Int J Biochem Cell Biol. 2015 Oct;67:139-47. doi: 10.1016/j.biocel.2015.04.004. Epub 2015 Apr 20.

Abstract

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.

Keywords: Chromatin; DNA methylation; Development; Genomic imprinting; Non-coding RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genomic Imprinting
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Mice
  • Muscular Dystrophy, Facioscapulohumeral / genetics*
  • Muscular Dystrophy, Facioscapulohumeral / metabolism
  • Muscular Dystrophy, Facioscapulohumeral / pathology
  • Organ Specificity
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • Histones
  • RNA, Untranslated