Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development

Ryutaro Hirasawa, Hatsune Chiba, Masahiro Kaneda, Shoji Tajima, En Li, Rudolf Jaenisch, Hiroyuki Sasaki

Research output: Contribution to journalArticle

317 Citations (Scopus)

Abstract

Parental origin-specific DNA methylation regulates the monoallelic expression of the mammalian imprinted genes. The methylation marks or imprints are established in the parental germline and maintained throughout embryonic development. However, it is unclear how the methylation imprints are maintained through extensive demethylation in cleavage-stage preimplantation embryos. Previous reports suggested that DNA methyltransferase(s) other than Dnmt1 is involved in the maintenance of the imprints during cleavage. Here we demonstrate, by using conditional knockout mice, that the other known DNA methyltransferases Dnmt3a and Dnmt3b are dispensable for the maintenance of the methylation marks at most imprinted loci. We further demonstrate that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of all imprinted loci examined in blastocysts. Consistent with these results we find that zygotic Dnmt1 is expressed in the preimplantation embryo. Thus, contrary to the previous reports, Dnmt1 alone is sufficient to maintain the methylation marks of the imprinted genes.

Original languageEnglish
Pages (from-to)1607-1616
Number of pages10
JournalGenes and Development
Volume22
Issue number12
DOIs
Publication statusPublished - Jun 15 2008
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this