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TitleJARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications.
Journal, issue, pagesScience, Vol. 371, Issue 6527, Year 2021
Publish dateJan 22, 2021
AuthorsVignesh Kasinath / Curtis Beck / Paul Sauer / Simon Poepsel / Jennifer Kosmatka / Marco Faini / Daniel Toso / Ruedi Aebersold / Eva Nogales /
PubMed AbstractPolycomb 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 ...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.
External linksScience / PubMed:33479123 / PubMed Central
MethodsEM (single particle)
Resolution3.5 Å
Structure data

21707

6wkr

EMDB-21707, PDB-6wkr:
PRC2-AEBP2-JARID2 bound to H2AK119ub1 nucleosome
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
KeywordsGENE REGULATION/DNA / chromatin / nucleosome / transcription / cryo-EM / ubiquitination / gene regulation-DNA complex / heterochromatin / DNA binding

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