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XB-ART-57863
Science 2021 Jan 22;3716527:. doi: 10.1126/science.abc3393.
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JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications.

Kasinath V , Beck C , Sauer P , Poepsel S , Kosmatka J , Faini M , Toso D , Aebersold R , Nogales E .


Abstract
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.

PubMed ID: 33479123
PMC ID: PMC7993630
Article link: Science
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: eed ezh2 h2ac21 h2bc21 jarid2 prc1

References [+] :
Adams, PHENIX: building new software for automated crystallographic structure determination. 2002, Pubmed