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Genome wide mapping of histone methylation reveals a distinct epigenomic signature in human pluripotent stem cells
Author(s) -
Hitchler Michael James,
Veerappan Chendhore,
Aman Joseph,
Fox Victoria,
Cuningham Cynthia,
Van Den Berg David,
Berman Benjamin,
Pera Martin,
Laird Peter,
Rice Judd C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.833.11
Subject(s) - epigenomics , h3k4me3 , biology , induced pluripotent stem cell , embryonic stem cell , bivalent chromatin , histone , chromatin , genetics , epigenetics , cellular differentiation , histone methylation , microbiology and biotechnology , gene , dna methylation , chromatin remodeling , gene expression , promoter
In human pluripotent stem cell cultures, differentiation‐associated genes are silenced but “poised” for expression by bivalent chromatin marks: the concurrent presence of activating (H3K4me3) and repressing (H3K27me3) histone modifications. Here we sought to map this bivalent state across the genome of a subset of heterogeneous cultured human embryonic stem cells; the fraction that expresses the highest amounts of pluripotency‐associated factors (hpESCs). To this end, ChIP‐Seq was performed for H3K4me3 and H3K27me3 in hpESCs and the heterogeneous culture from which they were purified. Consistent with previous reports, both populations displayed high levels of H3K27me3 at differentiation‐associated genes. While H3K4me3 was also abundant at differentiation‐associated genes in the heterogeneous culture, this histone modification was generally absent at these genes in hpESCs. Therefore, our findings indicate that hpESCs possess a distinct epigenomic signature that typically lacks bivalent domains and that the repression of differentiation‐associated genes is regulated primarily by Polycomb. Collectively, our results strongly suggest that bivalency represents a transitory state between pluripotent and lineage committed cells.