The myogenin gene is activated during myocyte differentiation by pre-existing, not newly synthesized transcription factor MEF-2

Abstract

The myogenin gene, a member of the gene family encoding muscle-specific basic-helix-loop-helix transcription factors, is activated in myoblasts at the onset of differentiation and can be induced in fibroblasts by forced expression of MyoD or its relatives. Here, we report that a small proximal promoter region of the Myf-4 gene, the human myogenin homolog, suffices to direct muscle-specific expression and up-regulation by MyoD. The minimal promoter contains an E-box and a MEF-2 consensus element. Paradoxically, we find that the MEF-2 binding site but not the E-box is necessary for cell type-specific expression and activation by MyoD in tissue culture cells. This suggests an activating mechanism which is independent of direct protein interactions at the E-box. MEF-2 binding complexes were detected in myoblasts and myotubes, as well as in fibroblasts with no strict correlation to myogenin expression. Moreover, transcription of myogenin could be induced in the presence of potent inhibitors of protein synthesis. From these results we conclude that myogenin expression is not mediated primarily through de novo synthesis of MEF-2 but rather involves a post-translational mode of activation.