Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks

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• 作者：Frank  ; W. Schmitges¹ ; ⁶ ; Archana  ; B. Prusty² ; ⁶ ; Mahamadou Faty¹ ; Alexandra Stü ; tzer³ ; Gondichatnahalli  ; M. Lingaraju¹ ; Jonathan Aiwazian¹ ; Ragna Sack¹ ; Daniel Hess¹ ; Ling Li⁴ ; Shaolian Zhou⁴ ; Richard  ; D. Bunker¹ ; Urs Wirth⁵ ; Tewis Bouwmeester⁵ ; Andreas Bauer⁵ ; Nga Ly-Hartig² ; Kehao Zhao⁴ ; Homan Chan⁴ ; Justin Gu⁴ ; Heinz Gut¹ ; Wolfgang Fischle³ ; Jü ; rg Mü ; ller² ; ⁷ ; ^{muellerj@biochem.mpg.de"" rel=""nofollow} ; Nicolas  ; H. Thomä ; ¹ ; ^{nicolas.thoma@fmi.ch"" rel=""nofollow}
• 刊名：Molecular Cell
• 出版年：2011
• 出版时间：6 May 2011
• 年：2011
• 卷：42
• 期：3
• 页码：330-341
• 全文大小：1525 K

文摘

Summary

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 overwriting active chromatin domains.