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Papers In Press, published online ahead of print June 1, 2000
Institute of Pathology, University Hospital RWTH Aachen, D-52074 Aachen D-52074
Corresponding Author: Buettner{at}pat.rwth-aachen.de
Caveolin-3 protein is the only member of the caveolin family that shows a unique muscle specific expression pattern, and loss of its functional activity causes muscular dystrophy. Caveolin-3 mRNA levels are dramatically increased during the formation of myotubes in the C2C12 cell line. In this study, we characterized the human caveolin-3 5? flanking region. Promoter deletion assays and mutational analysis demonstrate that the proximal E box element is sufficient to control caveolin-3 gene transcription. Myogenic basic helix-loop-helix transcription factors are known to interact with E-box elements and to activate the entire myogenic program during skeletal muscle myogenesis. Transient transfection assays indicated that overexpression of myogenin activates caveolin-3 reporter gene expression, whereas Id2 overexpression inhibited caveolin-3 promoter activation by myogenin. A mutant Id2 protein lacking the HLH domain was not capable of suppressing myogenin mediated activation. Determination of caveolin-3 transcript distribution patterns in vivo revealed that mRNA was first detectable at day 10 of gestation in the developing somites and heart. Caveolin-3 protein in myoblasts and myotubes was expressed in both the plasma membrane and vesicular structures. During skeletal myogenesis the level of Id2, an inhibitor of differentiation, decreases, allowing the induced bHLH transcription factor myogenin to form transcriptionally active heterodimers that bind to the caveolin-3 promoter and thereby mediate its transcription.
J. Biol. Chem, 10.1074/jbc.M001430200
Submitted on February 22, 2000
Revised on May 8, 2000
Accepted on June 1, 2000
The basic helix-loop-helix transcription factors myogenin and Id2 mediate specific induction of the caveolin-3 gene expression during embryonic development(Title revised)
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