CTCF regulates asynchronous replication of the imprinted H19/Igf2 domain

Cell Cycle. 2007 Feb 15;6(4):450-4. doi: 10.4161/cc.6.4.3854. Epub 2007 Feb 12.

Abstract

Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/Igf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/Igf2 domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Binding Sites
  • CCCTC-Binding Factor
  • Chromosomes, Mammalian
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Genomic Imprinting*
  • Inheritance Patterns / physiology
  • Insulin-Like Growth Factor II / chemistry
  • Insulin-Like Growth Factor II / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis, Site-Directed
  • RNA, Long Noncoding
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / genetics*
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • S Phase / genetics
  • S Phase / physiology*

Substances

  • CCCTC-Binding Factor
  • Ctcf protein, mouse
  • DNA-Binding Proteins
  • H19 long non-coding RNA
  • IGF2 protein, mouse
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Repressor Proteins
  • Insulin-Like Growth Factor II