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PMID: 19767730 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Role of the polycomb protein EED in the propagation of repressive histone marks.

Nature ·Vol. 461 ·No. 7265 ·2009-10-08 ·Pages 762-7

Margueron R, Justin N, Ohno K, Sharpe ML, Son J, Drury WJ, Voigt P, Martin SR, Taylor WR, De Marco V, Pirrotta V, Reinberg D, Gamblin SJ

Abstract

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.

MeSH Terms
Allosteric Regulation Animals Cell Line Chromatin/chemistry,genetics,metabolism Crystallography, X-Ray Drosophila Proteins/chemistry,genetics,metabolism Drosophila melanogaster/genetics,growth & development,metabolism Enzyme Activation Gene Silencing Histone-Lysine N-Methyltransferase/chemistry,metabolism Histones/chemistry,metabolism Lysine/analogs & derivatives,metabolism Methylation Models, Biological Models, Molecular Nuclear Proteins/metabolism Nucleosomes/chemistry,genetics,metabolism Polycomb Repressive Complex 2 Protein Binding Protein Structure, Tertiary Repressor Proteins/chemistry,genetics,metabolism Substrate Specificity
Chemicals
Chromatin Drosophila Proteins EED protein, Drosophila Histones Nuclear Proteins Nucleosomes Repressor Proteins trimethyllysine E(z) protein, Drosophila Histone-Lysine N-Methyltransferase PRC2 protein, Drosophila Polycomb Repressive Complex 2 esc protein, Drosophila Lysine
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Margueron Raphael
Howard Hughes Medical Institute and Department of Biochemistry, New York University Medical School, 522 First Avenue, New York, New York 10016, USA.
Justin Neil
Ohno Katsuhito
Sharpe Miriam L
Son Jinsook
Drury William J
Voigt Philipp
Martin Stephen R
Taylor William R
De Marco Valeria
Pirrotta Vincenzo
Reinberg Danny
Gamblin Steven J
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature08398
Published
2009-10-08
Epub
2009-00-20
Pages
762-7
Language
English
Region
England
NLM ID
0410462
PMCID
PMC3772642
Subset
IM
Grants
NIGMS NIH HHS · R01 GM064844-08 · United States
NIGMS NIH HHS · R01 GM037120 · United States
Medical Research Council · MC_U117584222 · United Kingdom
NIGMS NIH HHS · R37 GM037120 · United States
NIGMS NIH HHS · GM064844 · United States
NIGMS NIH HHS · GM37120 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM064844 · United States
Databases
PDB
3IIW, 3IIY, 3IJ0, 3IJ1, 3IJC
External Links
PubMed source DOI: 10.1038/nature08398 PMC Full Text View journal details
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