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Histone methylation by PRC2 is inhibited by active chromatin marks

Wirth, Urs and Bouwmeester, Antonius and Bauer, Andreas and Thoma, Nicolas and Schmidges, Frank W. and Prusty, Archana B. and Faty, Mahamadou and Stützer, Alexandra and Lingaraju, Gondihcathhanlli M. and Aiwazian, Jonathan and Sack, Ragna and Hess, Daniel and Li, ling and Zhou, Shalolian and Bunker, Richard D. and Wirth, Urs and Ly-Hartig, Nga and Zhao, Kehao and Chan, Homan and Gu, Justin and Gut, Heinz and Fischle, Wolfgang and Müller, Jürg and Thomä, Nicolas H. (2011) Histone methylation by PRC2 is inhibited by active chromatin marks. Molecular Cell, 42 (3). pp. 330-341. ISSN 1097-2765

Abstract

The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through deposition of histone H3 lysine 27 tri-methyl (H3-K27me3) modifications. Here, we analyzed the molecular mechanism by which PRC2 recognizes and discriminates between transcriptionally repressed and active chromatin. We show structurally and biochemically that the unmodified histone H3 tail comprising residues 1-14 is bound by the PRC2 Nurf55-Su(z)12 sub-complex. We find that H3-K4me3 modified tails are no longer retained by Nurf55-Su(z)12, and that H3-K4me3 triggers allosteric PRC2 inhibition in conjunction with the Su(z) VEFS domain and E(z). Inhibition requires H3-K4me3 to be on the same tail as H3-K27. The PRC2 HMTase activity is also inhibited by H3-K36me2/3, but not by the heterochromatin mark such as H3-K9me3. Inhibition by H3-K4me3 and H3-K36me2/3 marks of transcriptionally active chromatin is conserved in mammalian and fly PRC2. In the case of the diverse plant PRC2 complexes, the specific Su(z)12 subunit present determines whether the complex is inhibited by these active chromatin marks. PRC2 inhibition by active chromatin marks, coupled with PRC2 stimulation by transcriptionally repressive H3-K27me3, enables PRC2 to autonomously template repressive marks H3-K27me3 without overwriting active chromatin domains.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: PRC2
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/4138

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