6WKR

PRC2-AEBP2-JARID2 bound to H2AK119ub1 nucleosome

Summary for 6WKR

• Entry DOI: 10.2210/pdb6wkr/pdb
• EMDB information: 21707
• Descriptor: Ubiquitin, Histone H4, Histone H2A type 1, ... (15 entities in total)
• Functional Keywords: chromatin, nucleosome, transcription, cryo-em, ubiquitination, gene regulation-dna complex, heterochromatin, dna binding, gene regulation/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 18
• Total formula weight: 623906.75

Authors

Kasinath, V.,Nogales, E.,Beck, C.,Sauer, P.,Poepsel, S.,Kosmatka, J.,Faini, M.,Toso, D.,Aebersold, R. (deposition date: 2020-04-16, release date: 2021-02-03, Last modification date: 2025-06-04)

Primary citation

Kasinath, V.,Beck, C.,Sauer, P.,Poepsel, S.,Kosmatka, J.,Faini, M.,Toso, D.,Aebersold, R.,Nogales, E.
JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications.
Science, 371:-, 2021

PubMed 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: 33479123
DOI: 10.1126/science.abc3393

Experimental method

ELECTRON MICROSCOPY (3.5 Å)