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TitleStructural basis for PRC2 decoding of active histone methylation marks H3K36me2/3.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateNov 19, 2020
AuthorsKsenia Finogenova / Jacques Bonnet / Simon Poepsel / Ingmar B Schäfer / Katja Finkl / Katharina Schmid / Claudia Litz / Mike Strauss / Christian Benda / Jürg Müller /
PubMed AbstractRepression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 ...Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomes . Accordingly, H3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin.
External linksElife / PubMed:33211010 / PubMed Central
MethodsEM (single particle)
Resolution4.4 - 5.24 Å
Structure data

11910

7at8

EMDB-11910, PDB-7at8:
Histone H3 recognition by nucleosome-bound PRC2 subunit EZH2.
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-11912:
Cryo-EM map of PHF1-PRC2 on a heterodimeric dinucleosome.
Method: EM (single particle) / Resolution: 5.24 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsGENE REGULATION / Polycomb / nucleosome / histone methyltransferase / PRC2 / EZH2 / H3K36 / H3 tail / H3 / histone H3 / Polycomb Repressive Complex 2 / cryo-EM / nucleosome recognition / H3K36me2 / H3K36me3

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