Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3
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- Ksenia Finogenova
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
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- Jacques Bonnet
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
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- Simon Poepsel
- California Institute for Quantitative Biology (QB3), University of California, California Institute for Quantitative Biology (QB3), Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States
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- Ingmar B Schäfer
- Max Planck Institute of Biochemistry, Department of Structural Cell Biology, Martinsried, Germany
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- Katja Finkl
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
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- Katharina Schmid
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
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- Claudia Litz
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
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- Mike Strauss
- Max Planck Institute of Biochemistry, cryoEM Facility, Martinsried, Germany
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- Christian Benda
- Max Planck Institute of Biochemistry, Department of Structural Cell Biology, Martinsried, Germany
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- Jürg Müller
- Max Planck Institute of Biochemistry, Laboratory of Chromatin Biology, Martinsried, Germany
説明
<jats:p>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<jats:italic>in vitro</jats:italic>. Accordingly,<jats:italic>Drosophila</jats:italic>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.</jats:p>
収録刊行物
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- eLife
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eLife 9 2020-11-19
eLife Sciences Publications, Ltd
