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Am J Physiol Cell Physiol 287: C1031-C1040, 2004. First published June 9, 2004; doi:10.1152/ajpcell.00492.2003
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Molecular analysis of fiber type-specific expression of murine myostatin promoter

Mônica Senna Salerno, Mark Thomas, Davanea Forbes, Trevor Watson, Ravi Kambadur, and Mridula Sharma

Animal Genomics, AgResearch, Hamilton, and Ovita Limited, Dunedin, New Zealand

Submitted 7 November 2003 ; accepted in final form 31 May 2004

Myostatin is a negative regulator of muscle growth, and absence of the functional myostatin protein leads to the heavy muscle phenotype in both mouse and cattle. Although the role of myostatin in controlling muscle mass is established, little is known of the mechanisms regulating the expression of the myostatin gene. In this study, we have characterized the murine myostatin promoter in vivo. Various constructs of the murine myostatin promoter were injected into the quadriceps muscle of mice, and the reporter luciferase activity was analyzed. The results indicate that of the seven E-boxes present in the 2.5-kb fragment of the murine myostatin promoter, the E5 E-box plays an important role in the regulation of promoter activity in vivo. Furthermore, the in vitro studies demonstrated that MyoD preferentially binds and upregulates the murine myostatin promoter activity. We also analyzed the activity of the bovine and murine promoters in murine skeletal muscle and showed that, despite displaying comparable levels of activity in murine myoblast cultures, bovine myostatin promoter activity is much weaker than murine myostatin promoter in mice. Finally, we demonstrate that in vivo, the 2.5-kb region of the murine myostatin promoter is sufficient to drive the activity of the reporter gene in a fiber type-specific manner.

myogenic regulatory factor; E-box; naked DNA


Address for reprint requests and other correspondence: M. Sharma, Animal Genomics, AgResearch, Ruakura Research Centre, Private Bag 3123, East St., Hamilton, New Zealand (E-mail: mridula.sharma{at}agresearch.co.nz)




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D. L. Allen and T. G. Unterman
Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C188 - C199.
[Abstract] [Full Text] [PDF]


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