PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes.
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.
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Zhonghua
Z
Gao
Jin
J
Zhang
Roberto
R
Bonasio
Francesco
F
Strino
Ayana
A
Sawai
Fabio
F
Parisi
Yuval
Y
Kluger
Danny
D
Reinberg
D002454:Cell Differentiation; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058732:Embryoid Bodies / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism / Q000648:ultrastructure; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D040901:Proteomics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
C570479:CBX2 protein, human; C503627:CBX7 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D009707:Nucleosomes; D063146:Polycomb-Group Proteins; C434957:RYBP protein, human; D012097:Repressor Proteins; C104531:YAF2 protein, human; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; D044767:Ubiquitin-Protein Ligases