Universität zu Köln

Finogenova, Ksenia ORCID: 0000-0002-7512-8637, Bonnet, Jacques, Poepsel, Simon, Schaefer, Ingmar B., Finkl, Katja, Schmid, Katharina, Litz, Claudia, Strauss, Mike, Benda, Christian and Mueller, Juerg (2020). Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. eLife, 9. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Finogenova, Ksenia UNSPECIFIED orcid.org/0000-0002-7512-8637 UNSPECIFIED Bonnet, Jacques UNSPECIFIED UNSPECIFIED UNSPECIFIED Poepsel, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Ingmar B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Finkl, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Litz, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Strauss, Mike UNSPECIFIED UNSPECIFIED UNSPECIFIED Benda, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Juerg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-311069
DOI:	10.7554/eLife.61964
Journal or Publication Title:	eLife
Volume:	9
Date:	2020
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOSOME CORE PARTICLE; POLYCOMB GROUP PROTEINS; METHYLTRANSFERASE ACTIVITY; CRYO-EM; DROSOPHILA-MELANOGASTER; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; TUDOR DOMAIN; CHROMATIN; COMPLEX Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31106