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TitleStructures of human PRC2 with its cofactors AEBP2 and JARID2.
Journal, issue, pagesScience, Vol. 359, Issue 6378, Page 940-944, Year 2018
Publish dateFeb 23, 2018
AuthorsVignesh Kasinath / Marco Faini / Simon Poepsel / Dvir Reif / Xinyu Ashlee Feng / Goran Stjepanovic / Ruedi Aebersold / Eva Nogales /
PubMed AbstractTranscriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron ...Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.
External linksScience / PubMed:29348366 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 4.6 Å
Structure data

7334

6c23

EMDB-7334, PDB-6c23:
Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in the Compact Active State
Method: EM (single particle) / Resolution: 3.9 Å

7335

6c24

EMDB-7335, PDB-6c24:
Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in the Extended Active State
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-7337:
Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in the Extended Basal state
Method: EM (single particle) / Resolution: 4.6 Å

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / polycomb repressive complex / AEBP2 / JARID2 / histone modification

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