JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications

被引：136

作者：

Kasinath, Vignesh ^{[1
]}

Beck, Curtis ^{[2
]}

Sauer, Paul ^{[1
,3
]}

Poepsel, Simon ^{[4
,5
,6
]}

Kosmatka, Jennifer ^{[2
]}

Faini, Marco ^{[7
]}

Toso, Daniel ^{[1
]}

Aebersold, Ruedi ^{[7
,8
]}

Nogales, Eva ^{[1
,2
,3
,9
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, QB3 Inst, 229 Stanley Hall, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA

[4] Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany

[5] Univ Cologne, Univ Hosp, Cologne, Germany

[6] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany

[7] Swiss Fed Inst Technol, Dept Biol, Inst Mol Syst Biol, Zurich, Switzerland

[8] Univ Zurich, Fac Sci, Zurich, Switzerland

[9] Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA

来源：

SCIENCE | 2021年 / 371卷 / 6527期

关键词：

STRUCTURAL BASIS; POLYCOMB; CHROMATIN; RECRUITMENT; COMPLEX; METHYLATION; INHIBITION; EFFICIENT; PROTEIN; ROBUST;

D O I：

10.1126/science.abc3393

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo-electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and the H2AK119-ubiquitin, whereas AEBP2 has an additional scaffolding role. The presence of these cofactors partially overcomes the inhibitory effect that H3K4me3 and H3K36me3 exert on core PRC2 (in the absence of cofactors). Our results support a key role for JARID2 and AEBP2 in the cross-talk between histone modifications and PRC2 activity.

引用

页码：362 / +

页数：35

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