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

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. Overall design: Through a global survey DMVs in different species and different developmental stages , we validated DMVs play important role in gene regulation and development. Further studying different types of DMVs in vivo, Polycomb-target DMVs are more enriched TFs. Next, we continue to finding out what roles Polycomb plays in maintenance hypomethylation of DMVs and how it regulates DNA methylation in DMVs.