Role of the polycomb protein Eed in the propagation of repressive histone marks

By R. Margueron, N. Justin, K. Ohno, M. Sharpe, J. Son, W. Drury, P. Voigt, S. Martin, William R. Taylor, V. De Marco and 3 more. Nature, 2009

1,174 citations recorded by the source corpus.

Polycomb group proteins have an essential role in the epigenetic maintenance of repressive chromatin states. The gene-silencing activity of the Polycomb repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and disrupt development. These findings suggest a model for the propagation of the H3K27me3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8c609aa136f878716ba04062c2c9db4319824f1d

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Citations in the corpus

Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa (2010, background): “This interaction was shown to stimulate the enzymatic activity of PRC2 toward H3K27 and to be essential for early Drosophila melanogaster developmen”
Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation (2014, background): “A series of auxiliary proteins, including SUZ12 and EED, associate with EZH1/2 and modulate targeting, chromatin binding, and catalytic activity (Cao and Zhang, 2004; Ketel et al., 2005; Margueron et al., 2009; Pasini et al., 2004).”
Control of Embryonic Stem Cell State (2011, background): “PcG complexes can associate with nucleosomes with histone H3K9me3 (Margueron et al., 2009) and further contribute to repression through mechanisms described below.”
The Polycomb Complex PRC2 and its Mark in Life (2011, background): “74 ); (3) the interaction of EED with the product of PRC2 catalysis, H3K27me3 (ref”
Chromatin Structure and the Inheritance of Epigenetic Information (2010, background): “EED is responsible for the specific recognition of trimethylated repressive lysines by PRC2, although other components of this complex contribute to the overall affinity for nucleosome”
Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. (2011, neutral): “Biotinylated peptides, H3 (1-21) (#12-403), H3 (21-44) (#12-404), H3(21-44)K27(me1) (#12-567), H3(21-44)K27(me2) (#12566), and H3(21-44)K27(me3) (#12-565), were purchased from Upstate Biotechnology.”
MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures (2015, neutral): “Input signal [0–39]”
Chromatin replication and epigenome maintenance (2012, background): “and EZH2 binds H3K27me3 as part of polycomb repressive complex 2 (PRC2”
Epigenetic plasticity and the hallmarks of cancer (2017, background): “Polycomb repression can be maintained through mitotic cell division by several mechanisms, including a conformational switch in the EZH2 complex that is stimulated byH3K27 methylated histones and results in increased enzyme activity (17).”
Histone methylation by PRC2 is inhibited by active chromatin marks. (2011, background): “Previous studies reported that addition of H3K27me3 peptides in trans enhances H3K27 methylation of oligonucleosomes by human PRC2 through binding to the EED WD40 domain (Margueron et al., 2009; Xu et al., 2010).”
Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”