title: EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos.
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.
authors.affiliation: CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
authors.forename: Ghislain
authors.initials: G
authors.lastname: Auclair
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Borgel
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Lionel A
authors.initials: LA
authors.lastname: Sanz
authors.affiliation: CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
authors.forename: Judith
authors.initials: J
authors.lastname: Vallet
authors.affiliation: CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
authors.forename: Sylvain
authors.initials: S
authors.lastname: Guibert
authors.affiliation: CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
authors.forename: Michael
authors.initials: M
authors.lastname: Dumas
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cavelier
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Girardot
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Forné
authors.affiliation: Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.affiliation: CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
mesh_terms: D026924:Amino Acid Transport System A / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology; D017422:Sequence Analysis, DNA
chemical_list: D026924:Amino Acid Transport System A; C420522:Slc38a4 protein, mouse; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase