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PMID: 20300060 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis.

The EMBO journal ·Vol. 29 ·No. 8 ·2010-04-21 ·Pages 1401-11

Seenundun S, Rampalli S, Liu QC, Aziz A, Palii C, Hong S, Blais A, Brand M, Ge K, Dilworth FJ

Abstract

Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue-specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone H3-Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3-Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Interestingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene.

MeSH Terms
Animals Cell Line Creatine Kinase/metabolism Genes Histone Demethylases/metabolism Histones/metabolism Homeodomain Proteins/metabolism Methylation Mice Muscle Development Myoblasts/cytology,metabolism Myogenin/genetics Nuclear Proteins/metabolism RNA Polymerase II/antagonists & inhibitors,metabolism Trans-Activators/metabolism
Chemicals
Histones Homeodomain Proteins Myogenin Nuclear Proteins Six4 protein, mouse Trans-Activators Histone Demethylases Utx protein, mouse Creatine Kinase RNA Polymerase II
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Seenundun Shayesta
Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Rampalli Shravanti
Liu Qi-Cai
Aziz Arif
Palii Carmen
Hong SunHwa
Blais Alexandre
Brand Marjorie
Ge Kai
Dilworth Francis Jeffrey
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2010.37
Published
2010-04-21
Epub
2010-00-18
Pages
1401-11
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2868576
Subset
IM
Grants
NIDDK NIH HHS · ZIADK047055-03 · United States
Intramural NIH HHS · ZIA DK075003-08 · United States
CIHR · Canada
NIDDK NIH HHS · ZIADK075017-01 · United States
NIDDK NIH HHS · ZIADK075003-06 · United States
Intramural NIH HHS · Z01 DK047055-01 · United States
Intramural NIH HHS · Z01 DK075003-04 · United States
Intramural NIH HHS · Z01 DK047055-02 · United States
Intramural NIH HHS · Z99 DK999999 · United States
Intramural NIH HHS · Z01 DK075003-05 · United States
Intramural NIH HHS · ZIA DK075017-03 · United States
External Links
PubMed source DOI: 10.1038/emboj.2010.37 PMC Full Text View journal details
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