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

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

October 2008 | Volume 4 | Issue 10 | e1000242 | 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
This study investigates the structure and function of bivalent chromatin domains in embryonic stem (ES) cells, which are marked by overlapping repressive (H3K27me3) and activating (H3K4me3) histone modifications. Using chromatin immunoprecipitation and ultra-high-throughput sequencing, the authors map key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) in human and mouse ES cells. They identify two classes of bivalent domains: those occupied by both PRC2 and PRC1 (PRC1-positive) and those specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains are functionally distinct, showing greater conservation of chromatin state, efficient retention of repressive marks upon differentiation, and association with developmental regulator gene promoters. Computational genomics reveals that the locations, sizes, and motif contents of CpG islands can predict the genomewide localization of PRC2, PRC1, and bivalent domains. The study proposes that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting both PRC2 and PRC1 during early embryogenesis.This study investigates the structure and function of bivalent chromatin domains in embryonic stem (ES) cells, which are marked by overlapping repressive (H3K27me3) and activating (H3K4me3) histone modifications. Using chromatin immunoprecipitation and ultra-high-throughput sequencing, the authors map key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) in human and mouse ES cells. They identify two classes of bivalent domains: those occupied by both PRC2 and PRC1 (PRC1-positive) and those specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains are functionally distinct, showing greater conservation of chromatin state, efficient retention of repressive marks upon differentiation, and association with developmental regulator gene promoters. Computational genomics reveals that the locations, sizes, and motif contents of CpG islands can predict the genomewide localization of PRC2, PRC1, and bivalent domains. The study proposes that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting both PRC2 and PRC1 during early embryogenesis.
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