| A model for transmission of the H3K27me3 epigenetic mark. | |
| | |
MedLine Citation:
|
PMID: 18931660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 |
Affiliation:
|
Biotech Research & Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N., Denmark. klaus.hansen@bric.dk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Carrier Proteins
/
genetics,
metabolism Catalysis Cell Line Cells, Cultured Chromatin / genetics, metabolism DNA-Binding Proteins / genetics, metabolism* Epigenesis, Genetic* Fibroblasts / metabolism G1 Phase / physiology Genes, Reporter Histones / genetics, metabolism* Humans Kidney / cytology Luciferases / metabolism Lysine / genetics, metabolism Methylation Models, Biological* Mutation Nuclear Proteins / genetics, metabolism Promoter Regions, Genetic RNA, Small Interfering / metabolism Repressor Proteins / genetics, metabolism S Phase / physiology Transcription Factors / genetics, metabolism* Transfection |
| Chemical | |
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 |
| Comments/Corrections | |
Erratum In:
|
Nat Cell Biol. 2008 Dec;10(12):1484 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility.
Next Document: Scaffolding function of PAK in the PDK1-Akt pathway.