Document Detail


A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation.
MedLine Citation:
PMID:  21694756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In proliferating myoblasts, muscle specific genes are silenced by epigenetic modifications at their promoters, including histone H3K9 methylation. Derepression of the promoter of the gene encoding the myogenic factor myogenin (Myog) is key for initiation of muscle differentiation. The mechanism of H3K9 demethylation at the Myog promoter is unclear, however. Here, we identify an isoform of the histone demethylase JMJD2A/KDM4A that lacks the N-terminal demethylase domain (ΔN-JMJD2A). The amount of ΔN-JMJD2A increases during differentiation of C2C12 myoblasts into myotubes. Genome-wide expression profiling and exon-specific siRNA knockdown indicate that, in contrast to the full-length protein, ΔN-JMJD2A is necessary for myotube formation and muscle-specific gene expression. Moreover, ΔN-JMJD2A promotes MyoD-induced conversion of NIH3T3 cells into muscle cells. ChIP-on-chip analysis indicates that ΔN-JMJD2A binds to genes mainly involved in transcriptional control and that this binding is linked to gene activation. ΔN-JMJD2A is recruited to the Myog promoter at the onset of differentiation. This binding is essential to promote the demethylation of H3K9me2 and H3K9me3. We conclude that induction of the ΔN-JMJD2A isoform is crucial for muscle differentiation: by directing the removal of repressive chromatin marks at the Myog promoter, it promotes transcriptional activation of the Myog gene and thus contributes to initiation of muscle-specific gene expression.
Authors:
Laure Verrier; Fabrice Escaffit; Catherine Chailleux; Didier Trouche; Marie Vandromme
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-02
Journal Detail:
Title:  PLoS genetics     Volume:  7     ISSN:  1553-7404     ISO Abbreviation:  PLoS Genet.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-22     Completed Date:  2011-11-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  101239074     Medline TA:  PLoS Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001390     Citation Subset:  IM    
Affiliation:
Université de Toulouse, UPS, LBCMCP, F-31062, Toulouse, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation*
Cells, Cultured
Chromatin / metabolism
Epigenesis, Genetic
Histone Demethylases / genetics,  metabolism,  physiology*
Humans
Mice
Muscle, Skeletal / cytology*,  metabolism
Myoblasts / cytology,  metabolism
NIH 3T3 Cells
Protein Isoforms / genetics,  metabolism
Transfection
Chemical
Reg. No./Substance:
0/Chromatin; 0/Protein Isoforms; EC 1.14.11.-/Histone Demethylases; EC 1.14.11.-/JMJD2A protein, mouse
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