MLL1 is required for PAX7 expression and satellite cell self-renewal in mice

Gregory C. Addicks, Caroline E. Brun, Marie-Claude Sincennes, John Saber, Christopher J. Porter, A. Francis Stewart, Patricia Ernst and Michael A. Rudnicki ()
Additional contact information
Gregory C. Addicks: Ottawa Hospital Research Institute
Caroline E. Brun: Ottawa Hospital Research Institute
Marie-Claude Sincennes: Ottawa Hospital Research Institute
John Saber: Ottawa Hospital Research Institute
Christopher J. Porter: Ottawa Hospital Research Institute
A. Francis Stewart: Technische Universität Dresden
Patricia Ernst: University of Colorado/Anschutz Medical Campus
Michael A. Rudnicki: Ottawa Hospital Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract PAX7 is a paired-homeobox transcription factor that specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. We previously found that PAX7 recruits the H3K4 methyltransferases MLL1/2 to epigenetically activate target genes. Here we report that in the absence of Mll1, myoblasts exhibit reduced H3K4me3 at both Pax7 and Myf5 promoters and reduced Pax7 and Myf5 expression. Mll1-deficient myoblasts fail to proliferate but retain their differentiation potential, while deletion of Mll2 had no discernable effect. Re-expression of PAX7 in committed Mll1 cKO myoblasts restored H3K4me3 enrichment at the Myf5 promoter and Myf5 expression. Deletion of Mll1 in satellite cells reduced satellite cell proliferation and self-renewal, and significantly impaired skeletal muscle regeneration. Pax7 expression was unaffected in quiescent satellite cells but was markedly downregulated following satellite cell activation. Therefore, MLL1 is required for PAX7 expression and satellite cell function in vivo. Furthermore, PAX7, but not MLL1, is required for Myf5 transcriptional activation in committed myoblasts.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12086-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12086-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12086-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().