The ontogeny of allele-specific methylation associated with imprinted genes in the mouse

Michael Brandeis*, Tal Kafri, Mira Ariel, J. Richard Chaillet, John McCarrey, Aharon Razin, Howard Cedar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

298 Scopus citations

Abstract

We have investigated the DNA methylation patterns in genomically imprinted genes of the mouse. Both Igf2 and H19 are associated with clear-cut regions of allele-specific paternal modification in late embryonic and adult tissues. By using a sensitive PCR assay, it was possible to follow the methylation state of individual HpaII sites in these genes through gametogenesis and embryogenesis. Most of these CpG moieties are not differentially modified in the mature gametes and also become totally demethylated in the early embryo in a manner similar to non-imprinted endogenous genes. Thus, the overall allele-specific methylation pattern at these sites must be established later during embryogenesis after the blastula stage. In contrast, sites in an Igf2r gene intron and one CpG residue in the Igf2 upstream region have allele-specific modification patterns which are established either in the gametes or shortly after fertilization and are preserved throughout pre-implantation embryogenesis. These studies suggest that only a few DNA modifications at selective positions in imprinted genes may be candidates for playing a role in the maintenance of parental identity during development.

Original languageEnglish
Pages (from-to)3669-3677
Number of pages9
JournalEMBO Journal
Volume12
Issue number9
StatePublished - 1993

Keywords

  • Embryogenesis
  • Gametogenesis
  • Imprinting
  • Methylation

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