Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity

Thomas Dahlet, Andrea Argüeso Lleida, Hala Al Adhami, Michael Dumas, Ambre Bender, Richard P. Ngondo, Manon Tanguy, Judith Vallet, Ghislain Auclair, Anaïs F. Bardet and Michael Weber ()
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Thomas Dahlet: University of Strasbourg
Andrea Argüeso Lleida: University of Strasbourg
Hala Al Adhami: University of Strasbourg
Michael Dumas: University of Strasbourg
Ambre Bender: University of Strasbourg
Richard P. Ngondo: University of Strasbourg
Manon Tanguy: University of Strasbourg
Judith Vallet: University of Strasbourg
Ghislain Auclair: University of Strasbourg
Anaïs F. Bardet: University of Strasbourg
Michael Weber: University of Strasbourg

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Mouse embryos acquire global DNA methylation of their genome during implantation. However the exact roles of DNA methyltransferases (DNMTs) in embryos have not been studied comprehensively. Here we systematically analyze the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos. We find a strict division of function between DNMT1, responsible for maintenance methylation, and DNMT3A/B, solely responsible for methylation acquisition in development. By analyzing severely hypomethylated embryos, we uncover multiple functions of DNA methylation that is used as a mechanism of repression for a panel of genes including not only imprinted and germline genes, but also lineage-committed genes and 2-cell genes. DNA methylation also suppresses multiple retrotransposons and illegitimate transcripts from cryptic promoters in transposons and gene bodies. Our work provides a thorough analysis of the roles of DNA methyltransferases and the importance of DNA methylation for transcriptome integrity in mammalian embryos.

Date: 2020
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DOI: 10.1038/s41467-020-16919-w

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