Asynchronous replication of imprinted genes is established in the gametes and maintained during development

Nature. 1999 Oct 28;401(6756):929-32. doi: 10.1038/44866.


Genomic imprinting is characterized by allele-specific expression of multiple genes within large chromosomal domains that undergo DNA replication asynchronously during S phase. Here we show, using both fluorescence in situ hybridization analysis and S-phase fractionation techniques, that differential replication timing is associated with imprinted genes in a variety of cell types, and is already present in the pre-implantation embryo soon after fertilization. This pattern is erased before meiosis in the germ line, and parent-specific replication timing is then reset in late gametogenesis in both the male and female. Thus, asynchronous replication timing is established in the gametes and maintained throughout development, indicating that it may function as a primary epigenetic marker for distinguishing between the parental alleles.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Autoantigens / genetics
  • Cell Line
  • Cell Line, Transformed
  • DNA Methylation
  • DNA Replication*
  • Embryonic Development
  • Female
  • Genomic Imprinting*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oogenesis
  • Ovum / physiology*
  • Polymerase Chain Reaction
  • Pregnancy
  • Ribonucleoproteins, Small Nuclear*
  • S Phase
  • Spermatogenesis
  • Spermatozoa / physiology*
  • snRNP Core Proteins


  • Autoantigens
  • Ribonucleoproteins, Small Nuclear
  • snRNP Core Proteins