EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

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 r...

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Published inGenome research Vol. 26; no. 2; pp. 192 - 202
Main Authors Auclair, Ghislain, Borgel, Julie, Sanz, Lionel A, Vallet, Judith, Guibert, Sylvain, Dumas, Michael, Cavelier, Patricia, Girardot, Michael, Forné, Thierry, Feil, Robert, Weber, Michael
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.02.2016
Subjects
Amino Acid Transport System A - genetics
Animals
Biochemistry, Molecular Biology
Cells, Cultured
DNA Methylation
Embryo, Mammalian - metabolism
Female
Gene Expression
Gene Expression Regulation, Developmental
Gene Silencing
Histone-Lysine N-Methyltransferase - physiology
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mouse Embryonic Stem Cells - physiology
Sequence Analysis, DNA
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Summary: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.
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PMCID: PMC4728372
Present address: Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA
These authors contributed equally to this work.
Present address: MRC Clinical Sciences Centre, Imperial College London Faculty of Medicine, Hammersmith Hospital Campus, London W12 0NN, UK
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.198291.115