Author:
Auclair Ghislain,Borgel Julie,Sanz Lionel A.,Vallet Judith,Guibert Sylvain,Dumas Michael,Cavelier Patricia,Girardot Michael,Forné Thierry,Feil Robert,Weber Michael
Abstract
The extent to which histone modifying enzymes contribute to DNA methylation in mammals remains unclear. Previous studies suggested a link between the lysine methyltransferase EHMT2 (also known as G9A and KMT1C) and DNA methylation in the mouse. Here, we used a model of knockout mice to explore the role of EHMT2 in DNA methylation during mouse embryogenesis. The Ehmt2 gene is expressed in epiblast cells but is dispensable for global DNA methylation in embryogenesis. In contrast, EHMT2 regulates DNA methylation at specific sequences that include CpG-rich promoters of germline-specific genes. These loci are bound by EHMT2 in embryonic cells, are marked by H3K9 dimethylation, and have strongly reduced DNA methylation in Ehmt2−/− embryos. EHMT2 also plays a role in the maintenance of germline-derived DNA methylation at one imprinted locus, the Slc38a4 gene. Finally, we show that DNA methylation is instrumental for EHMT2-mediated gene silencing in embryogenesis. Our findings identify EHMT2 as a critical factor that facilitates repressive DNA methylation at specific genomic loci during mammalian development.
Funder
Agence National de Recherche
Institut National du Cancer
Association pour la Recherche contre le Cancer
International Cancer Research
MEDDTL
European Research Council
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
61 articles.
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