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MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element

Charge, Sophie B., Brack, Andrew S., Bayol, Stephanie A. and Hughes, Simon M. 2008, MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element, BMC developmental biology, vol. 8, pp. 1-13, doi: 10.1186/1471-213X-8-5.

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Title MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element
Author(s) Charge, Sophie B.
Brack, Andrew S.
Bayol, Stephanie A.
Hughes, Simon M.
Journal name BMC developmental biology
Volume number 8
Article ID 5
Start page 1
End page 13
Total pages 13
Publisher BioMed Central
Place of publication London, England
Publication date 2008
ISSN 1471-213X
Keyword(s) MyoD
transcription factor
adult muscle gene expression
satellite myoblasts
proximal enhancer/promoter (DRR/PRR)
innervated fibres
Summary Background
MyoD is a transcription factor implicated in the regulation of adult muscle gene expression. Distinguishing the expression of MyoD in satellite myoblasts and muscle fibres has proved difficult in vivo leading to controversy over the significance of MyoD expression within adult innervated muscle fibres. Here we employ the MD6.0-lacZ transgenic mouse, in which the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD drives lacZ, to show that MyoD is present and transcriptionally active in many adult muscle fibres.

Results

In culture, MD6.0-lacZ expresses in myotubes but not myogenic cells, unlike endogenous MyoD. Reporter expression in vivo is in muscle fibre nuclei and is reduced in MyoD null mice. The MD6.0-lacZ reporter is down-regulated both in adult muscle fibres by denervation or muscle disuse and in cultured myotubes by inhibition of activity. Activity induces and represses MyoD through the DRR and PRR, respectively. During the postnatal period, accumulation of β-galactosidase correlates with maturation of innervation. Strikingly, endogenous MyoD expression is up-regulated in fibres by complete denervation, arguing for a separate activity-dependent suppression of MyoD requiring regulatory elements outside the DRR/PRR.

Conclusion
The data show that MyoD regulation is more complex than previously supposed. Two factors, MyoD protein itself and fibre activity are required for essentially all expression of the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD in adult fibres. We propose that modulation of MyoD positive feedback by electrical activity determines the set point of MyoD expression in innervated fibres through the DRR/PRR element.
Language eng
DOI 10.1186/1471-213X-8-5
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30063113

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.