title: CpG island erosion, polycomb occupancy and sequence motif enrichment at bivalent promoters in mammalian embryonic stem cells.
abstract: In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a 'poised' state for subsequent activation or silencing during differentiation. We collected eleven pairs (H3K4me3 and H3K27me3) of ChIP sequencing datasets in human ES cells and eight pairs in murine ES cells, and predicted high-confidence (HC) bivalent promoters. Over 85% of H3K27me3 marked promoters were bivalent in human and mouse ES cells. We found that (i) HC bivalent promoters were enriched for developmental factors and were highly likely to be differentially expressed upon transcription factor perturbation; (ii) murine HC bivalent promoters were occupied by both polycomb repressive component classes (PRC1 and PRC2) and grouped into four distinct clusters with different biological functions; (iii) HC bivalent and active promoters were CpG rich while H3K27me3-only promoters lacked CpG islands. Binding enrichment of distinct sets of regulators distinguished bivalent from active promoters. Moreover, a 'TCCCC' sequence motif was specifically enriched in bivalent promoters. Finally, this analysis will serve as a resource for future studies to further understand transcriptional regulation during embryonic development.
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Mantsoki
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Devailly
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
authors.forename: Anagha
authors.initials: A
authors.lastname: Joshi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice; D059372:Nucleotide Motifs / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II