TY - JOUR
T1 - PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes
AU - Gao, Zhonghua
AU - Zhang, Jin
AU - Bonasio, Roberto
AU - Strino, Francesco
AU - Sawai, Ayana
AU - Parisi, Fabio
AU - Kluger, Yuval
AU - Reinberg, Danny
N1 - Funding Information:
We thank B. Bernstein, R. Koche, and other members of the Bernstein lab for great advice and helpful discussion on ChIP-seq; G. Felsenfeld for providing insulator sequences; V. Bardwell and C. Fry for providing reagents; D. Beck and P. Voigt for vector construction; T. Iwahara and W. Tee for providing RT primers; H. Zheng for MS analysis; the NYULMC Genome Technology Center for deep sequencing service; and P. Trojer for comments on the manuscript. This work is supported by grants from the National Institute of Health (GM-64844 and R37-37120), and the Howard Hughes Medical Institute (to D.R.). R.B. was supported by a Helen Hay Whitney Foundation post-doctoral fellowship. F.P. and Y.K. were partially supported by the Yale SPORE in Skin Cancer funded by the National Cancer Institute (P50-CA121974, R. Halaban, PI). Y.K. is supported by a grant from the National Institute of Health (CA-16359). F.S. was supported by the American-Italian Cancer Foundation (Post-Doctoral Research Fellowship).
PY - 2012/2/10
Y1 - 2012/2/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2012.01.002
DO - 10.1016/j.molcel.2012.01.002
M3 - Article
C2 - 22325352
AN - SCOPUS:84863011309
SN - 1097-2765
VL - 45
SP - 344
EP - 356
JO - Molecular cell
JF - Molecular cell
IS - 3
ER -