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  Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3

Finogenova, K., Bonnet, J., Poepsel, S., Schäfer, I. B., Finkl, K., Schmid, K., et al. (2020). Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. eLife, 9: e61964. doi:10.7554/eLife.61964.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-D3E6-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-D3E7-6
Genre: Journal Article

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 Creators:
Finogenova, Ksenia1, Author              
Bonnet, Jacques1, Author              
Poepsel, Simon2, Author
Schäfer, Ingmar B.3, Author              
Finkl, Katja1, Author              
Schmid, Katharina1, Author              
Litz, Claudia1, Author              
Strauss, Mike4, Author              
Benda, Christian3, Author              
Müller, Jürg1, Author              
Affiliations:
1Müller, Jürg / Chromatin Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565161              
2external, ou_persistent22              
3Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              
4Scientific Service Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565170              

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Free keywords: NUCLEOSOME CORE PARTICLE; POLYCOMB GROUP PROTEINS; METHYLTRANSFERASE ACTIVITY; CRYO-EM; DROSOPHILA-MELANOGASTER; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; TUDOR DOMAIN; CHROMATIN; COMPLEXLife Sciences & Biomedicine - Other Topics;
 Abstract: 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 in vitro. Accordingly, Drosophila 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 30
 Publishing info: -
 Table of Contents: Acknowledgements
We thank Eva Nogales for generous advice, sharing of expertise and for hosting KF for grid preparation. We thank Tom Cech for stimulating discussions. We thank JR Prabu for excellent computing support, S Uebel, E.Weyher, R Kim and A Yeroslaviz of the MPIB core facilities and Martin Spitaler and Giovannie Cardone of the MPIB imaging facility for excellent technical support and S Schkoelziger and S Schmähling for help with some of the experiments. This work was supported by the Deutsche Forschungsgemeinschaft (SFB1064) and the MPG. ChIP-seq data have been deposited in GEO (accession number: GSE148254). The structural data are deposited in the EMDB (EMD-11910 and EMD-11912) and PDB (7AT8).
 Rev. Type: -
 Identifiers: ISI: 000599345600001
DOI: 10.7554/eLife.61964
 Degree: -

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Project name : SFB1064
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Funding organization : Deutsche Forschungsgemeinschaft

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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 9 Sequence Number: e61964 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X