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Mapping Promoter CpG Methylation in mESCs

ABSTRACT: DNA methylation and histone modifications influence gene activities in a variety of mammalian cells. We report here the large scale mapping of DNA methylation patterns at proximal promoter regions in mouse embryonic stem cells (mESCs). A majority of methylated genes represent cell differentiation-associated genes that are repressed in mESCs. In contrast, unmethylated genes include many housekeeping and pluripotency genes such as STAT3 and Oct4/Nanog/Sox2, which are essential for ESC self-renewal. By comparing methylation patterns to the binding domains of Oct4/Nanog, Polycomb proteins, and histone H3 lysine (K) 4/27 trimethylation on gene promoters, we found that promoter DNA methylation is frequently the only epigenetic marker associated with a subset of silenced genes in mESCs that do not possess H3 K4/K27 trimethylation marks and are free from the binding of Polycomb proteins and the Oct4/Nanog transcription factors. Gene expression profiling of demethylated mESCs showed that a majority of up-regulated genes, including a subset of X-linked genes and many development genes, represent a distinct population of genes that are neither targeted by Polycomb and Oct4/Nanog, nor carry H3 K4/K27 trimethylation marks. Our data suggest that promoter methylation patterns in mESCs represent a unique epigenetic program that complements other regulatory mechanisms to allow the expression of pluripotency genes, but represses a subset of genes that will only be activated in specific cell lineages upon cell differentiation. Keywords: DNA Methylation, methylated DNA immunoprecipitation

ORGANISM(S): Mus musculus

PROVIDER: GSE9172 | GEO | 2008/01/28

SECONDARY ACCESSION(S): PRJNA102733

REPOSITORIES: GEO

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