Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-01

AUTHORS

Iain W McKinnell, Jeff Ishibashi, Fabien Le Grand, Vincent G J Punch, Gregory C Addicks, Jack F Greenblatt, F Jeffrey Dilworth, Michael A Rudnicki

ABSTRACT

Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme. More... »

PAGES

77-84

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb1671

DOI

http://dx.doi.org/10.1038/ncb1671

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033670056

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18066051


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