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

Mayssa H. Mokalled, Aaron N. Johnson, Esther E. Creemers, Eric N. Olson

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 andMRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury andmuscular 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.

Original languageEnglish (US)
Pages (from-to)190-202
Number of pages13
JournalGenes and Development
Volume26
Issue number2
DOIs
StatePublished - Jan 15 2012

Fingerprint

Regeneration
Cell Differentiation
Skeletal Muscle
Muscles
Skeletal Muscle Satellite Cells
Muscle Development
Wounds and Injuries
Stem Cells
Cell Proliferation
Population
myocardin

Keywords

  • MASTR
  • MEF2
  • MRTF-A
  • Muscle regeneration
  • MyoD
  • Satellite cells

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration. / Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

In: Genes and Development, Vol. 26, No. 2, 15.01.2012, p. 190-202.

Research output: Contribution to journalArticle

Mokalled, Mayssa H. ; Johnson, Aaron N. ; Creemers, Esther E. ; Olson, Eric N. / MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration. In: Genes and Development. 2012 ; Vol. 26, No. 2. pp. 190-202.
@article{d22d52145d724d6b881b559b5cf3ae34,
title = "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 andMRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury andmuscular 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.",
keywords = "MASTR, MEF2, MRTF-A, Muscle regeneration, MyoD, Satellite cells",
author = "Mokalled, {Mayssa H.} and Johnson, {Aaron N.} and Creemers, {Esther E.} and Olson, {Eric N.}",
year = "2012",
month = "1",
day = "15",
doi = "10.1101/gad.179663.111",
language = "English (US)",
volume = "26",
pages = "190--202",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",

}

TY - JOUR

T1 - MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

AU - Mokalled, Mayssa H.

AU - Johnson, Aaron N.

AU - Creemers, Esther E.

AU - Olson, Eric N.

PY - 2012/1/15

Y1 - 2012/1/15

N2 - 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 andMRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury andmuscular 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.

AB - 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 andMRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury andmuscular 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.

KW - MASTR

KW - MEF2

KW - MRTF-A

KW - Muscle regeneration

KW - MyoD

KW - Satellite cells

UR - http://www.scopus.com/inward/record.url?scp=84856291604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856291604&partnerID=8YFLogxK

U2 - 10.1101/gad.179663.111

DO - 10.1101/gad.179663.111

M3 - Article

C2 - 22279050

AN - SCOPUS:84856291604

VL - 26

SP - 190

EP - 202

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 2

ER -