Methylation at mouse Cdkn1c is acquired during postimplantation development and functions to maintain imprinted expression

Genomics. 2004 Dec;84(6):961-70. doi: 10.1016/j.ygeno.2004.08.004.

Abstract

Monoallelic expression of imprinted genes is generally associated with differential methylation. Methylation may be inherited as the gametic imprinting mark or may be acquired postfertilization. Here, we characterize a differentially methylated region associated with the mouse Cdkn1c gene and find that it is confined to a CpG island that begins 600 bp 5' of the promoter and extends into the transcription unit. Our analysis indicates that methylation of this region is not inherited from sperm, is acquired specifically on the paternal allele following implantation, and is dependent on KvDMR1. We further demonstrate that although methylation is required for maintaining silencing of the paternal Cdkn1c allele, it is not a prerequisite for the establishment of monoallelic expression at this locus. Prior to the onset of differential methylation, additional epigenetic modifications must play a role in distinguishing the parental alleles of Cdkn1c and influencing their expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • CpG Islands / genetics*
  • Cyclin-Dependent Kinase Inhibitor p57
  • DNA Methylation*
  • Embryo Implantation
  • Embryonic Development / physiology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Gene Silencing / physiology
  • Genomic Imprinting / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • Spermatozoa / growth & development
  • Spermatozoa / metabolism

Substances

  • Cdkn1c protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p57
  • Nuclear Proteins