Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks

被引：546

作者：

Schmitges, Frank W. ^{[1
]}

Prusty, Archana B. ^{[2
]}

Faty, Mahamadou ^{[1
]}

Stuetzer, Alexandra ^{[3
]}

Lingaraju, Gondichatnahalli M. ^{[1
]}

Aiwazian, Jonathan ^{[1
]}

Sack, Ragna ^{[1
]}

Hess, Daniel ^{[1
]}

Li, Ling ^{[4
]}

Zhou, Shaolian ^{[4
]}

Bunker, Richard D. ^{[1
]}

Wirth, Urs ^{[5
]}

Bouwmeester, Tewis ^{[5
]}

Bauer, Andreas ^{[5
]}

Ly-Hartig, Nga ^{[2
]}

Zhao, Kehao ^{[4
]}

Chan, Homan ^{[4
]}

Gu, Justin ^{[4
]}

Gut, Heinz ^{[1
]}

Fischle, Wolfgang ^{[3
]}

Mueller, Juerg ^{[2
]}

Thomae, Nicolas H. ^{[1
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[2] EMBL Heidelberg, Genome Biol Unit, D-69117 Heidelberg, Germany

[3] Max Planck Inst Biophys Chem, Lab Chromatin Biochem, D-37077 Gottingen, Germany

[4] China Novartis Inst Biomed Res, Shanghai, Peoples R China

[5] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland

来源：

MOLECULAR CELL | 2011年 / 42卷 / 03期

关键词：

EMBRYONIC STEM-CELLS; FLOWERING-LOCUS-C; METHYLTRANSFERASE ACTIVITY; STRUCTURAL BASIS; DROSOPHILA-MELANOGASTER; LYSINE-27; METHYLATION; RECOMBINANT HISTONES; CRYSTAL-STRUCTURE; POLYCOMB; COMPLEX;

D O I：

10.1016/j.molcel.2011.03.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2 Nurf55-Su(z)12 submodule. Binding of H3 is lost if lysine 4 in H3 is trimethylated. We find that H3K4me3 inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12 C terminus. In addition to H3K4me3, PRC2 is inhibited by H3K36me2/3 (i.e., both H3K36me2 and H3K36me3). Direct PRC2 inhibition by H3K4me3 and H3K36me2/3 active marks is conserved in humans, mouse, and fly, rendering transcriptionally active chromatin refractory to PRC2 H3K27 trimethylation. While inhibition is present in plant PRC2, it can be modulated through exchange of the Su(z)12 subunit. Inhibition by active chromatin marks, coupled to stimulation by transcriptionally repressive H3K27me3, enables PRC2 to autonomously template repressive H3K27me3 without over-writing active chromatin domains.

引用

页码：330 / 341

页数：12

共 53 条

[1] RETRACTED: Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1 (Retracted article. See vol. 521, pg. 110, 2015) [J].

Beisel, C ;

Imhof, A ;

Greene, J ;

Kremmer, E ;

Sauer, F .

NATURE, 2002, 419 (6909) :857-862

[2] Transcription-coupled methylation of histone H3 at lysine 36 regulates dosage compensation by enhancing recruitment of the MSL complex in Drosophila melanogaster [J].

Bell, Oliver ;

Conrad, Thomas ;

Kind, Jop ;

Wirbelauer, Christiane ;

Akhtar, Asifa ;

Schuebeler, Dirk .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (10) :3401-3409

[3] A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].

Bernstein, BE ;

Mikkelsen, TS ;

Xie, XH ;

Kamal, M ;

Huebert, DJ ;

Cuff, J ;

Fry, B ;

Meissner, A ;

Wernig, M ;

Plath, K ;

Jaenisch, R ;

Wagschal, A ;

Feil, R ;

Schreiber, SL ;

Lander, ES .

CELL, 2006, 125 (02) :315-326

[4]

Birve A, 2001, DEVELOPMENT, V128, P3371

[5] Role of histone H3 lysine 27 methylation in polycomb-group silencing [J].

Cao, R ;

Wang, LJ ;

Wang, HB ;

Xia, L ;

Erdjument-Bromage, H ;

Tempst, P ;

Jones, RS ;

Zhang, Y .

SCIENCE, 2002, 298 (5595) :1039-1043

[6] Role of hPHF1 in H3K27 methylation and Hox gene silencing [J].

Cao, Ru ;

Wang, Hengbin ;

He, Jin ;

Erdjument-Bromage, Hediye ;

Tempst, Paul ;

Zhang, Yi .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (05) :1862-1872

[7] Binding of the MLL PHD3 Finger to Histone H3K4me3 Is Required for MLL-Dependent Gene Transcription [J].

Chang, Pei-Yun ;

Hom, Robert A. ;

Musselman, Catherine A. ;

Zhu, Li ;

Kuo, Alex ;

Gozani, Or ;

Kutateladze, Tatiana G. ;

Cleary, Michael L. .

JOURNAL OF MOLECULAR BIOLOGY, 2010, 400 (02) :137-144

[8] The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules [J].

Collins, Robert E. ;

Northrop, Jeffrey P. ;

Horton, John R. ;

Lee, David Y. ;

Zhang, Xing ;

Stallcup, Michael R. ;

Cheng, Xiaodong .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2008, 15 (03) :245-250

[9] Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal polycomb sites [J].

Czermin, B ;

Melfi, R ;

McCabe, D ;

Seitz, V ;

Imhof, A ;

Pirrotta, V .

CELL, 2002, 111 (02) :185-196

[10] In situ proteolysis for protein crystallization and structure determination [J].

Dong, Aiping ;

Xu, Xiaohui ;

Edward, Aled M. .

NATURE METHODS, 2007, 4 (12) :1019-1021

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