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 31, 2008 | 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
A genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3K27me3) and activating (H3K4me3) histone modifications mark the promoters of over 2,000 genes. Using chromatin immunoprecipitation followed by ultra high-throughput sequencing, the study maps key histone modifications and subunits of PRC1 and PRC2 in human and mouse ES cells. Bivalent domains are segregated into two classes: PRC1-positive domains, which are occupied by both PRC1 and PRC2, and PRC2-only domains, which are specifically bound by PRC2. PRC1-positive domains are functionally distinct, showing stronger conservation of chromatin state and association with developmental regulator gene promoters. Computational genomics reveals that the locations of PRC2 and PRC1 can be predicted from CpG island locations, sizes, and underlying motif contents. The study proposes that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting PRC1 and PRC2 in pluripotent cells. PRC1-positive domains are larger, more conserved, and retain H3K27me3 more efficiently during differentiation. They correspond to a majority of developmental regulator genes. PRC2-only domains are less conserved and correspond to non-developmental genes. The study also identifies sequence elements and motifs that predict PRC2 localization in ES cells. PRC2-positive CpG islands show an over-representation of repressor motifs and a depletion of activator motifs. PRC1 occupancy is associated with larger PRC2-positive CpG islands. The findings suggest that CpG islands play a central role in PRC2 recruitment and that the genomewide localization of PRC1 and PRC2 can be largely predicted from CpG island locations, sizes, and motif content. The study highlights the importance of DNA sequence in determining PcG complex localization and bivalent domains in ES cells. The results have implications for understanding development and epigenetic reprogramming.A genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3K27me3) and activating (H3K4me3) histone modifications mark the promoters of over 2,000 genes. Using chromatin immunoprecipitation followed by ultra high-throughput sequencing, the study maps key histone modifications and subunits of PRC1 and PRC2 in human and mouse ES cells. Bivalent domains are segregated into two classes: PRC1-positive domains, which are occupied by both PRC1 and PRC2, and PRC2-only domains, which are specifically bound by PRC2. PRC1-positive domains are functionally distinct, showing stronger conservation of chromatin state and association with developmental regulator gene promoters. Computational genomics reveals that the locations of PRC2 and PRC1 can be predicted from CpG island locations, sizes, and underlying motif contents. The study proposes that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting PRC1 and PRC2 in pluripotent cells. PRC1-positive domains are larger, more conserved, and retain H3K27me3 more efficiently during differentiation. They correspond to a majority of developmental regulator genes. PRC2-only domains are less conserved and correspond to non-developmental genes. The study also identifies sequence elements and motifs that predict PRC2 localization in ES cells. PRC2-positive CpG islands show an over-representation of repressor motifs and a depletion of activator motifs. PRC1 occupancy is associated with larger PRC2-positive CpG islands. The findings suggest that CpG islands play a central role in PRC2 recruitment and that the genomewide localization of PRC1 and PRC2 can be largely predicted from CpG island locations, sizes, and motif content. The study highlights the importance of DNA sequence in determining PcG complex localization and bivalent domains in ES cells. The results have implications for understanding development and epigenetic reprogramming.
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Understanding Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains