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Muscle Stem Cell Self Renewal is Regulated by Acetylation of PAX7

60 Pages Posted: 9 Jul 2019 Sneak Peek Status: Review Complete

See all articles by Marie-Claude Sincennes

Marie-Claude Sincennes

University of Ottawa - Sprott Center for Stem Cell Research

Caroline E. Brun

University of Ottawa - Sprott Center for Stem Cell Research

Tabitha Rosembert

University of Ottawa - Sprott Center for Stem Cell Research

John Saber

University of Ottawa - Sprott Center for Stem Cell Research

Yoh-ichi Kawabe

University of Ottawa - Sprott Center for Stem Cell Research

Michael A. Rudnicki

University of Ottawa - Sprott Center for Stem Cell Research

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Abstract

The transcription factor PAX7 is a critical regulator of satellite cell survival, self-renewal and proliferation. PAX7 protein is regulated by different post-translational modifications that affect its transcriptional activity, and consequently, influence muscle regeneration. Here, we report two novel acetylation sites on the PAX7 protein, which regulate its transcriptional activity and chromatin binding. Abolishing PAX7 acetylation using CRISPR/Cas9 mutant mice impairs muscle regeneration and leads to progressive satellite cell exhaustion. We identified molecular regulators of PAX7 acetylation, the acetyltransferase MYST1 as well as with the deacetylase SIRT2, both of which control PAX7 acetylation levels and PAX7 target gene expression in myoblasts. MYST1 and SIRT2 are also important players in regulating the balance between satellite stem cell symmetric versus asymmetric division, therefore controlling satellite cell expansion, self-renewal and commitment. Our data demonstrate that acetylation levels regulate PAX7 transcriptional activity and function in satellite cells.

Keywords: Skeletal muscle, Satellite cell, muscle stem cell, Pax7, Myst1, Sirt2, Acetylation, Transcriptional activation, Asymmetric cell division, regeneration, Metabolism

Suggested Citation

Sincennes, Marie-Claude and Brun, Caroline E. and Rosembert, Tabitha and Saber, John and Kawabe, Yoh-ichi and Rudnicki, Michael A., Muscle Stem Cell Self Renewal is Regulated by Acetylation of PAX7 (July 8, 2019). CELL-STEM-CELL-D-19-00439. Available at SSRN: https://ssrn.com/abstract=3416644 or http://dx.doi.org/10.2139/ssrn.3416644
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Marie-Claude Sincennes

University of Ottawa - Sprott Center for Stem Cell Research

Ottawa, Ontario
Canada

Caroline E. Brun

University of Ottawa - Sprott Center for Stem Cell Research

Ottawa, Ontario
Canada

Tabitha Rosembert

University of Ottawa - Sprott Center for Stem Cell Research

Ottawa, Ontario
Canada

John Saber

University of Ottawa - Sprott Center for Stem Cell Research

Ottawa, Ontario
Canada

Yoh-ichi Kawabe

University of Ottawa - Sprott Center for Stem Cell Research

Ottawa, Ontario
Canada

Michael A. Rudnicki (Contact Author)

University of Ottawa - Sprott Center for Stem Cell Research ( email )

Ottawa, Ontario
Canada

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