Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells
Yikai Huang,
Wukui Zhao,
Congcong Wang,
Yaru Zhu,
Mengjie Liu,
Huan Tong,
Yin Xia,
Qing Jiang,
Jinzhong Qin
Affiliations
Yikai Huang
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Wukui Zhao
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Congcong Wang
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Yaru Zhu
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Mengjie Liu
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Huan Tong
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China
Yin Xia
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
Qing Jiang
Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of the Medical School of Nanjing University, Nanjing, China
Jinzhong Qin
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China; Corresponding author
Summary: Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters. Additionally, decreased PRC1.6 chromatin occupancy was observed following loss of individual components (L3mbtl2, Pcgf6, and Max) of the complex. Our findings suggest that the recruitment of noncanonical PRC1.6 complex in ESCs might be the result of L3mbtl2’s interaction with multiple components of the complex. : Yikai et al. report that Polycomb group protein L3mbtl2 assembles a complex whose composition is conserved with the Drosophila PhoRC. L3mbtl2-mediated chromatin recruitment of a variant PRC1 requires cooperation among complex components. Keywords: Polycomb, PRC1, PRC1.6, L3mbtl2, Pcgf6, Max, Mga, PhoRC, Sfmbt, Ring1b
