Publication Date:
2002-09-28
Description:
Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, Ru -- Wang, Liangjun -- Wang, Hengbin -- Xia, Li -- Erdjument-Bromage, Hediye -- Tempst, Paul -- Jones, Richard S -- Zhang, Yi -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):1039-43. Epub 2002 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351676" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Carrier Proteins/isolation & purification/metabolism
;
Cell Cycle Proteins/metabolism
;
Chromatin/metabolism
;
DNA-Binding Proteins/genetics/metabolism
;
Drosophila
;
Drosophila Proteins/genetics/*metabolism
;
*Gene Silencing
;
Genes, Homeobox
;
HeLa Cells
;
*Histone-Lysine N-Methyltransferase
;
Histones/*metabolism
;
*Homeodomain Proteins
;
Humans
;
Lysine/*metabolism
;
Methylation
;
Methyltransferases/isolation & purification/metabolism
;
Nuclear Proteins/metabolism
;
Nucleosomes/metabolism
;
Peptide Mapping
;
Polycomb Repressive Complex 1
;
Polycomb Repressive Complex 2
;
Precipitin Tests
;
Protein Methyltransferases
;
Proteins/isolation & purification/metabolism
;
RNA Interference
;
Repressor Proteins/isolation & purification/metabolism
;
Response Elements
;
Temperature
;
*Transcription Factors
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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