2yb8
Crystal structure of Nurf55 in complex with Su(z)12Crystal structure of Nurf55 in complex with Su(z)12
Structural highlights
FunctionSUZ12_DROME Polycomb group (PcG) protein. While PcG proteins are generally required to maintain the transcriptionally repressive state of homeotic genes throughout development, this protein is specifically required during the first 6 hours of embryogenesis to establish the repressed state. Component of the Esc/E(z) complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The Esc/E(z) complex is necessary but not sufficient for the repression of homeotic target genes, suggesting that the recruitment of the distinct PRC1 complex is also required. Publication Abstract from PubMedThe 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. Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks.,Schmitges FW, Prusty AB, Faty M, Stutzer A, Lingaraju GM, Aiwazian J, Sack R, Hess D, Li L, Zhou S, Bunker RD, Wirth U, Bouwmeester T, Bauer A, Ly-Hartig N, Zhao K, Chan H, Gu J, Gut H, Fischle W, Muller J, Thoma NH Mol Cell. 2011 May 6;42(3):330-41. PMID:21549310[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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