Document Detail

A model for transmission of the H3K27me3 epigenetic mark.
MedLine Citation:
PMID:  18931660     Owner:  NLM     Status:  MEDLINE    
Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.
Klaus H Hansen; Adrian P Bracken; Diego Pasini; Nikolaj Dietrich; Simmi S Gehani; Astrid Monrad; Juri Rappsilber; Mads Lerdrup; Kristian Helin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-19
Journal Detail:
Title:  Nature cell biology     Volume:  10     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-03     Completed Date:  2008-12-10     Revised Date:  2008-12-24    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1291-300     Citation Subset:  IM    
Biotech Research & Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N., Denmark.
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MeSH Terms
Carrier Proteins / genetics,  metabolism
Cell Line
Cells, Cultured
Chromatin / genetics,  metabolism
DNA-Binding Proteins / genetics,  metabolism*
Epigenesis, Genetic*
Fibroblasts / metabolism
G1 Phase / physiology
Genes, Reporter
Histones / genetics,  metabolism*
Kidney / cytology
Luciferases / metabolism
Lysine / genetics,  metabolism
Models, Biological*
Nuclear Proteins / genetics,  metabolism
Promoter Regions, Genetic
RNA, Small Interfering / metabolism
Repressor Proteins / genetics,  metabolism
S Phase / physiology
Transcription Factors / genetics,  metabolism*
Reg. No./Substance:
0/Carrier Proteins; 0/Chromatin; 0/DNA-Binding Proteins; 0/EED protein, human; 0/EZH2 protein, human; 0/Histones; 0/Nuclear Proteins; 0/RNA, Small Interfering; 0/Repressor Proteins; 0/SUZ12 protein, human; 0/Transcription Factors; 0/polycomb group proteins; 56-87-1/Lysine; EC 1.13.12.-/Luciferases
Erratum In:
Nat Cell Biol. 2008 Dec;10(12):1484

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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