Epigenetic regulation of mammalian genomic imprinting

Curr Opin Genet Dev. 2004 Apr;14(2):188-95. doi: 10.1016/j.gde.2004.01.005.


Imprinted genes play important roles in development, and most are clustered in large domains. Their allelic repression is regulated by 'imprinting control regions' (ICRs), which are methylated on one of the two parental alleles. Non-histone proteins and nearby sequence elements influence the establishment of this differential methylation during gametogenesis. DNA methylation, histone modifications, and also polycomb group proteins are important for the somatic maintenance of imprinting. The way ICRs regulate imprinting differs between domains. At some, the ICR constitutes an insulator that prevents promoter-enhancer interactions, when unmethylated. At other domains, non-coding RNAs could be involved, possibly by attracting chromatin-modifying complexes. The latter silencing mechanism has similarities with X-chromosome inactivation.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins
  • Epigenesis, Genetic / physiology*
  • GTP-Binding Proteins / genetics
  • GTPase-Activating Proteins
  • Gene Expression Regulation / physiology
  • Genomic Imprinting / physiology*
  • Insulin-Like Growth Factor II / genetics
  • Mice
  • Receptor, IGF Type 2 / genetics
  • Repressor Proteins


  • Arhgap35 protein, mouse
  • DNA-Binding Proteins
  • GTPase-Activating Proteins
  • Receptor, IGF Type 2
  • Repressor Proteins
  • Insulin-Like Growth Factor II
  • GTP-Binding Proteins