The central role of EED in the orchestration of polycomb group complexes.
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.
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas 77030, USA [4] Cancer Center, Houston Methodist Research Institute, Houston, Texas 77030, USA.
Qi
Q
Cao
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Xiaoju
X
Wang
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30329, USA.
Meng
M
Zhao
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30329, USA.
Rendong
R
Yang
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Rohit
R
Malik
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Yuanyuan
Y
Qiao
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Anton
A
Poliakov
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Anastasia K
AK
Yocum
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Yong
Y
Li
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Wei
W
Chen
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Xuhong
X
Cao
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Xia
X
Jiang
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Arun
A
Dahiya
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Clair
C
Harris
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Felix Y
FY
Feng
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Sundeep
S
Kalantry
1] Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30329, USA [2] Center for Comprehensive Informatics, Emory University, Atlanta, Georgia 30329, USA.
Zhaohui S
ZS
Qin
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Saravana M
SM
Dhanasekaran
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [4] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [5] Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Arul M
AM
Chinnaiyan
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D055785:Gene Knockdown Techniques; D056426:Genetic Loci; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D016513:Mice, SCID; D008954:Models, Biological; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000906:Antibodies; C491488:EED protein, human; C107275:Eed protein, mouse; D006657:Histones; D063146:Polycomb-Group Proteins; D000076983:Histone Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases