Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes

Mol Cell. 2012 Sep 28;47(6):909-20. doi: 10.1016/j.molcel.2012.07.010. Epub 2012 Aug 16.


Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Cadherins / genetics*
  • DNA Methylation*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Fertilization
  • Genetic Testing
  • Genomic Imprinting*
  • Germ Cells / metabolism*
  • Mice
  • Oocytes / metabolism*
  • Pseudogenes
  • Sequence Analysis, DNA


  • Cadherins
  • M-cadherin

Associated data

  • GEO/GSE32687