PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes

• DOI: 10.1016/j.molcel.2012.01.002
• Publication Date: 2012-02-09T23:09:06Z
• Authors: Zhonghua Gao; Jin Zhang; Roberto Bonasio; Francesco Strino; Ayana Sawai; Fabio Parisi; Yuval Kluger; Danny Reinberg
• Keywords: Polycomb Repressive Complex 1; Proteomics; 0303 health sciences; Sequence Homology, Amino Acid; Chromosomal Proteins, Non-Histone; Intracellular Signaling Peptides and Proteins; Gene Expression; Muscle Proteins; Polycomb-Group Proteins; Cell Differentiation; Cell Biology; Nucleosomes; DNA-Binding Proteins; Histones; Repressor Proteins; 03 medical and health sciences; HEK293 Cells; Multiprotein Complexes; Humans; Promoter Regions, Genetic; Molecular Biology; Embryoid Bodies; Cell Proliferation; Protein Binding

The heterogeneous nature of mammalian PRC1 complexes has hindered our understanding of their biological functions. Here, we present a comprehensive proteomic and genomic analysis that uncovered six major groups of PRC1 complexes, each containing a distinct PCGF subunit, a RING1A/B ubiquitin ligase, and a unique set of associated polypeptides. These PRC1 complexes differ in their genomic localization, and only a small subset colocalize with H3K27me3. Further biochemical dissection revealed that the six PCGF-RING1A/B combinations form multiple complexes through association with RYBP or its homolog YAF2, which prevents the incorporation of other canonical PRC1 subunits, such as CBX, PHC, and SCM. Although both RYBP/YAF2- and CBX/PHC/SCM-containing complexes compact chromatin, only RYBP stimulates the activity of RING1B toward H2AK119ub1, suggesting a central role in PRC1 function. Knockdown of RYBP in embryonic stem cells compromised their ability to form embryoid bodies, likely because of defects in cell proliferation and maintenance of H2AK119ub1 levels.