Transactivation of capn2 by myogenic regulatory factors during myogenesis |
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Authors: | Dedieu Stéphane Mazères Germain Dourdin Nathalie Cottin Patrick Brustis Jean-Jacques |
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Affiliation: | Laboratoire Biosciences de l'Aliment, ISTAB-USC-INRA 429, Université Bordeaux I, Avenue des Facultés, 33405 Talence Cedex, France. |
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Abstract: | The calcium-activated cysteine protease m-calpain plays a pivotal role during the earlier stages of myogenesis, particularly during fusion. The enzyme is a heterodimer, encoded by the genes capn2, for the large subunit, and capn4, for the small subunit. To study the regulation of m-calpain, the DNA sequence upstream of capn2 was analyzed for promoter elements, revealing the existence of five consensus-binding sites (E-box) for several myogenic regulatory factors and one binding site for myocyte enhancer factor-2 (MEF-2). Transient transfections with reporter gene constructs containing the E-box revealed that MyoD presents a high level of transactivation of reporter constructs containing this region, in particular the sequences including the MEF-2/E4-box. In addition, over-expression of various myogenic factors demonstrated that MyoD and myogenin with much less efficiency, can up-regulate capn2, both singly and synergistically, while Myf5 has no effect on synthesis of the protease. Experiments with antisense oligonucleotides directed against each myogenic factor revealed that MyoD plays a specific and pivotal role during capn2 regulation, and cannot be replaced wholly by myogenin and Myf5. |
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Keywords: | calpain myogenesis MRF antisense over-expression |
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