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

• Published in: Molecular cell Vol. 45; no. 3; pp. 344 - 356
• Main Authors: Gao, Zhonghua, Zhang, Jin, Bonasio, Roberto, Strino, Francesco, Sawai, Ayana, Parisi, Fabio, Kluger, Yuval, Reinberg, Danny
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.02.2012
• Subjects: Cell Differentiation; Cell Proliferation; chromatin; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryoid Bodies - metabolism; embryonic stem cells; Gene Expression; genomics; HEK293 Cells; Histones - metabolism; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; mammals; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Nucleosomes - metabolism; Nucleosomes - ultrastructure; Polycomb Repressive Complex 1; Polycomb-Group Proteins; polypeptides; Promoter Regions, Genetic; Protein Binding; Proteomics; Repressor Proteins - genetics; Repressor Proteins - metabolism; Repressor Proteins - physiology; Sequence Homology, Amino Acid; ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2012.01.002

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. ► All PRC1 complexes are divided into six groups characterized by six PCGF subunits ► These six groups of PRC1 complexes target different genes through distinct mechanisms ► RYBP/YAF2 form mutually exclusive PRC1 complexes with CBX/PHC/SCM proteins ► RYBP stimulates PRC1-mediated H2AK119ub1 and is essential for ESC differentiation