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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.

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