MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration.

Abstract:

:In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process.

journal_name

Genes Dev

journal_title

Genes & development

authors

Mokalled MH,Johnson AN,Creemers EE,Olson EN

doi

10.1101/gad.179663.111

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

190-202

issue

2

eissn

0890-9369

issn

1549-5477

pii

26/2/190

journal_volume

26

pub_type

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