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


Journal article


Gregory C Addicks, Gregory C Addicks, Caroline E. Brun, Caroline E. Brun, Marie-Claude Sincennes, Marie-Claude Sincennes, J. Saber, J. Saber, C. J. Porter, A. F. Stewart, P. Ernst, Michael A. Rudnicki, Michael A. Rudnicki
Nature Communications, 2019

Semantic Scholar DOI PubMedCentral PubMed
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APA   Click to copy
Addicks, G. C., Addicks, G. C., Brun, C. E., Brun, C. E., Sincennes, M.-C., Sincennes, M.-C., … Rudnicki, M. A. (2019). MLL1 is required for PAX7 expression and satellite cell self-renewal in mice. Nature Communications.


Chicago/Turabian   Click to copy
Addicks, Gregory C, Gregory C Addicks, Caroline E. Brun, Caroline E. Brun, Marie-Claude Sincennes, Marie-Claude Sincennes, J. Saber, et al. “MLL1 Is Required for PAX7 Expression and Satellite Cell Self-Renewal in Mice.” Nature Communications (2019).


MLA   Click to copy
Addicks, Gregory C., et al. “MLL1 Is Required for PAX7 Expression and Satellite Cell Self-Renewal in Mice.” Nature Communications, 2019.


BibTeX   Click to copy

@article{gregory2019a,
  title = {MLL1 is required for PAX7 expression and satellite cell self-renewal in mice},
  year = {2019},
  journal = {Nature Communications},
  author = {Addicks, Gregory C and Addicks, Gregory C and Brun, Caroline E. and Brun, Caroline E. and Sincennes, Marie-Claude and Sincennes, Marie-Claude and Saber, J. and Saber, J. and Porter, C. J. and Stewart, A. F. and Ernst, P. and Rudnicki, Michael A. and Rudnicki, Michael A.}
}

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. PAX7 transcription factor specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. Here authors find that Mll1 deletion in myoblasts in mice results in reduced H3K4me3 at both Pax7 and Myf5 promoters, reduced Pax7 and Myf5 expression, and proliferation defects.


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