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

doi:10.1016/j.celrep.2018.02.072

Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells

Cell Rep. 2018 Mar 13;22(11):3032-3043. doi: 10.1016/j.celrep.2018.02.072.

Authors

Yikai Huang¹, Wukui Zhao¹, Congcong Wang¹, Yaru Zhu¹, Mengjie Liu¹, Huan Tong¹, Yin Xia², Qing Jiang³, Jinzhong Qin⁴

Affiliations

¹ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
² School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
³ Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of the Medical School of Nanjing University, Nanjing, China.
⁴ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China. Electronic address: qinjz@nicemice.cn.

PMID: 29539429
DOI: 10.1016/j.celrep.2018.02.072

Abstract

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.

Keywords: L3mbtl2; Max; Mga; PRC1; PRC1.6; Pcgf6; PhoRC; Polycomb; Ring1b; Sfmbt.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Embryonic Stem Cells / metabolism*
Genetic Variation / genetics*
Humans