Myocyte Enhancer Factor 2C and Myogenin Up-regulate Each Other's Expression and Induce the Development of Skeletal Muscle in P19 Cells*
- From the Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada
Abstract
Two families of transcription factors, myogenic regulatory factors (MRFs) and myocyte enhancer factor 2 (MEF2), function synergistically to regulate myogenesis. In addition to activating structural muscle-specific genes, MRFs and MEF2 activate each other's expression. The MRF, myogenin, can activate MEF2 DNA binding activity when transfected into fibroblasts and, in turn, the myogenin promoter contains essential MEF2 DNA binding elements. To determine which MEF2 is involved in this regulation, P19 cells stably expressing MyoD and myogenin were compared for their ability to activate the expression of MEF2 family members. There was very little cross-activation of MyoD expression by myogenin and vice versa. Myogenin expression, and not MyoD, was found to up-regulate MEF2C expression. MEF2A, -B, and -D expression levels were not up-regulated by overexpression of either MyoD or myogenin. To examine whether MEF2C can differentially regulate MyoD or myogenin expression, P19 cell lines overexpressing MEF2C were analyzed. MEF2C induced myogenesis in P19 cells and up-regulated the expression of myogenin with 25-fold greater efficiency than that of MyoD. Therefore, myogenin and MEF2C participate in a regulatory loop in differentiating stem cells. This positive regulation does not extend to MyoD or the other MEF2 family members. Consequently, MEF2C appears to play a specific role in early events of myogenesis.
Footnotes
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↵* This work was supported by a grant from the Medical Research Council of Canada.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Supported by a studentship from the Natural Sciences and Engineering Research Council of Canada.
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↵§ Supported by a Medical Research Council of Canada Scholarship (Development Grant). To whom correspondence should be addressed. Tel.: (519) 679-2111 (ext. 6867); Fax (519) 661-3175; E-mail: skerjanc@julian.uwo.ca.
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↵2 A. G. Ridgeway, S. Wilton, and I. S. Skerjanc, submitted for publication.
- Abbreviations:
- MEF2
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myocyte enhancer factor 2
- MRF
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myogenic regulatory factor
- PCR
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polymerase chain reaction
- RT
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reverse transcription
- kb
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kilobase pair(s)
- MHC
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myosin heavy chain
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- Received September 15, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
