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

Zhonghua Gao, Jin Zhang, Roberto Bonasio, Francesco Strino, Ayana Sawai, Fabio Parisi, Yuval Kluger, Danny Reinberg

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431 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)344-356
Number of pages13
JournalMolecular cell
Volume45
Issue number3
DOIs
StatePublished - Feb 10 2012

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Gao, Z., Zhang, J., Bonasio, R., Strino, F., Sawai, A., Parisi, F., Kluger, Y., & Reinberg, D. (2012). PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes. Molecular cell, 45(3), 344-356. https://doi.org/10.1016/j.molcel.2012.01.002