Targets and dynamics of promoter DNA methylation during early mouse development

Julie Borgel, Sylvain Guibert, Yufeng Li, Hatsune Chiba, Dirk Schübeler, Hiroyuki Sasaki, Thierry Forné, Michael Weber

Research output: Contribution to journalArticlepeer-review

419 Citations (Scopus)

Abstract

DNA methylation is extensively reprogrammed during the early phases of mammalian development, yet genomic targets of this process are largely unknown. We optimized methylated DNA immunoprecipitation for low numbers of cells and profiled DNA methylation during early development of the mouse embryonic lineage in vivo. We observed a major epigenetic switch during implantation at the transition from the blastocyst to the postimplantation epiblast. During this period, DNA methylation is primarily targeted to repress the germline expression program. DNA methylation in the epiblast is also targeted to promoters of lineage-specific genes such as hematopoietic genes, which are subsequently demethylated during terminal differentiation. De novo methylation during early embryogenesis is catalyzed by Dnmt3b, and absence of DNA methylation leads to ectopic gene activation in the embryo. Finally, we identify nonimprinted genes that inherit promoter DNA methylation from parental gametes, suggesting that escape of post-fertilization DNA methylation reprogramming is prevalent in the mouse genome.

Original languageEnglish
Pages (from-to)1093-1100
Number of pages8
JournalNature Genetics
Volume42
Issue number12
DOIs
Publication statusPublished - 2010 Dec

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Targets and dynamics of promoter DNA methylation during early mouse development'. Together they form a unique fingerprint.

Cite this