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A role of Polycomb in the maintenance of hypomethylation for DNA methylation valley

ABSTRACT: DNA methylation valleys (DMVs) are large loci that are devoid of DNA methylation in the genome. We show that DMVs are hypomethylated at most stages in development and are highly conserved across vertebrates. Importantly, DMVs are hotspots of regulatory regions for key developmental regulator genes. 4C-seq analyses indicate that DMVs are insulated and self-interacting domains. By analyzing a panel of DNA methylomes for the mouse tissues, we have identified a subset of DMVs that are dynamically methylated. These DMVs are strongly enriched by Polycomb and their histone substrate H3K27me3 when the associated genes are silenced, and surprisingly show elevated DNA methylation upon gene activation. In support of a role of Polycomb in DMV hypomethylation, we observed aberrant methylation in DMVs in mESCs deficient for Eed. Finally, we showed that Polycomb regulates hypomethylation of DMVs likely through TET proteins.

ORGANISM(S): Mus musculus

PROVIDER: GSE102753 | GEO | 2017/12/24

SECONDARY ACCESSION(S): PRJNA398611

REPOSITORIES: GEO

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