EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

Ghislain Auclair; Julie Borgel; Lionel A. Sanz; Judith Vallet; Sylvain Guibert; Michael Dumas; Patricia Cavelier; Michael Girardot; Thierry Forné; Robert Feil; Michael Weber

doi:10.1101/gr.198291.115

EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

¹CNRS, University of Strasbourg, UMR7242 Biotechnology and Cell Signaling, 67412 Illkirch, France;
²Institute of Molecular Genetics, CNRS UMR5535, University of Montpellier, 34293 Montpellier, France

Corresponding authors: robert.feil{at}igmm.cnrs.fr; michael.weber{at}unistra.fr

↵3 These authors contributed equally to this work.

↵4 Present address: MRC Clinical Sciences Centre, Imperial College London Faculty of Medicine, Hammersmith Hospital Campus, London W12 0NN, UK
↵5 Present address: Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA

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.

Footnotes

[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.198291.115.

Received August 13, 2015.
Accepted November 13, 2015.

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