Polycomb repressive complexes 1 and 2 (PRC1 and 2) play a critical role in the epigenetic regulation of transcription during cellular differentiation, stem cell pluripotency and neoplastic progression. Here we show that the polycomb group protein EED, a core component of PRC2, physically interacts with and functions as part of PRC1. Components of PRC1 and PRC2 compete for EED binding. EED functions to recruit PRC1 to H3K27me3 loci and enhances PRC1-mediated H2A ubiquitin E3 ligase activity. Taken together, we suggest an integral role for EED as an epigenetic exchange factor coordinating the activities of PRC1 and 2.
Bibliographical noteFunding Information:
We thank Dr Terry Magnuson for the Eed−/− mESCs cells, Cynthia Wang for protein purification, Ingrid J. Apel for AlphaScreen assays, Javed Siddiqui, Rui Wang, Wei Yan, Yaqing Zhang, Rong Zhao, Maria Chen, Kari Wilder-Romans for technical assistance, Terry Barrette for database management, the University of Michigan Vector Core for generating adenovirus and lentivirus, Ram Mani, J. Chad Brenner, Irfan A. Asangani for discussions, and Jyoti Athanikar and Karen Giles for critically reading the manuscript and submitting documents. The confocal immunofluorescence colocalization analysis was performed in the Microscopy and Image-analysis Laboratory (MIL) at the University of Michigan, Department of Cell & Developmental Biology. This work is supported in part by the Prostate SPORE P50CA69568 and National Institutes of Health (R01CA132874). A.M.C. is supported by the Prostate Cancer Foundation (PCF), the Doris Duke Charitable Foundation, and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor and A. Alfred Taubman Scholar. Q.C. is supported by the US Department of Defense (PC094725) and a Young Investigator Award from the PCF; F.Y.F. is supported by a Young Investigator Award from the PCF; S.K. is supported by an NIH Director’s New Innovator Award (DP2-OD-008646-01) and a March of Dimes Basil O’Connor Starter Scholar Research Award; M.Z. and Z.S.Q. are supported by National Institutes of Health (7R01HG005119-02).
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