The myogenin gene is activated during myocyte differentiation by pre-existing, not newly synthesized transcription factor MEF-2.
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.
Buchberger
A
A
Department of Cell and Molecular Biology, University of Braunschweig, Federal Republic of Germany.
Ragge
K
K
Arnold
H H
HH
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004640:Emetine / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D066298:In Vitro Techniques; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D017570:MyoD Protein / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics; D018008:Myogenin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; C503799:MYOG protein, human; D017570:MyoD Protein; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D012333:RNA, Messenger; D014157:Transcription Factors; C063403:myogenic factor 6; D003513:Cycloheximide; D004640:Emetine