Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains

• DOI: 10.1371/journal.pgen.1000242
• Publication Date: 2008-10-30T22:34:57Z
• Authors: Manching Ku; Richard P. Koche; Esther Rheinbay; Eric M. Mendenhall; Mitsuhiro Endoh; Tarjei S. Mikkelsen; Aviva Presser; Chad Nusbaum; Xiaohui Xie; Andrew S. Chi; Mazhar Adli; Simon Kasif; Leon M. Ptaszek; Chad A. Cowan; Eric S. Lander; Haruhiko Koseki; Bradley E. Bernstein
• Keywords: PRC2; Polycomb-group proteins; Bivalent (engine); Bivalent chromatin; CpG site; Chromatin immunoprecipitation

In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating 4 histone modifications mark the promoters of more than 2,000 genes. To gain insight into structure function domains, we mapped key subunits Polycomb-repressive complexes 1 2 (PRC1 PRC2) genomewide in human mouse ES cells by immunoprecipitation, followed ultra high-throughput sequencing. We find that can be segregated two classes—the first occupied both PRC2 PRC1 (PRC1-positive) second specifically bound (PRC2-only). PRC1-positive appear functionally distinct as they efficiently retain tri-methylation upon differentiation, show stringent conservation state, associate an overwhelming number developmental regulator gene promoters. also used computational genomics to search for sequence determinants Polycomb binding. This analysis revealed locations largely predicted from locations, sizes, underlying motif contents CpG islands. propose large islands depleted motifs confer epigenetic memory recruiting full repertoire pluripotent cells.