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

By Manching Ku, Richard P. Koche, Esther Rheinbay, E. Mendenhall, Mitsuhiro Endoh, Tarjei S. Mikkelsen, Aviva Presser, Chad Nusbaum, Xiaohui S. Xie, A. Chi and 7 more. PLoS Genetics, 2008

1,051 citations recorded by the source corpus.

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

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d8fb729b9f1c06f56095ecfef9dd1dfeddadb7dc

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Citations in the corpus

A double take on bivalent promoters. (2013, background): “Moreover, they exhibit larger regions of H3K27me3 and are more likely to remain repressed upon differentiation (Ku et al. 2008).”
seqMINER: an integrated ChIP-seq data interpretation platform (2010, methodology): “Over the last years, numerous studies have used ChIP-seq as a central method to create GW binding maps for a particular genomic feature (1,2), installing ChIP-seq as the gold standard in the functional genomics toolbox.”
PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes (2012, result): “This observation is in contrast with the extensive overlap between RING1B and H3K27me3 reported in ESCs (Boyer et al., 2006; Ku et al., 2008) but consistent with other studies that reported H3K27me3-independent recruitment of PRC1 to chromatin Figure 3.”
Mechanisms of Polycomb gene silencing: knowns and unknowns (2009, background): “In addition, PRC1 and PRC2 tend to be broadly distributed across many kilobases of mammalian developmental control gene”
Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells (2014, positive): “ChIP-seq assays were carried out on approximately 1 × 10 6 cells per histone modification and 10 7 cells per transcription factor, following the procedures outlined in (Ku et al., 2008; Mikkelsen et al., 2007).”
Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation (2014, background): “Nonmethylated DNA is generally concentrated in vertebrate regulatory elements called CpG islands, and most mammalian polycomb target sites are associated with CpG islands (Ku et al., 2008).”
Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. (2017, neutral): “MLL2 is responsible for H3K4 trimethylation at bivalent promoters in ESCs (Figure 2B) (Denissov et al., 2014), whereas MLL1 is required for H3K4 trimethylation at only a small subset of genes, including HOX genes, emphasizing the non-redundant function of these two histone methyltransferases.”