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J. Biol. Chem., Vol. 278, Issue 35, 33169-33174, August 29, 2003

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Specific Activation of the Acetylcholine Receptor Subunit Genes by MyoD Family Proteins^*

Frédéric Charbonnier, Bruno Della Gaspera, Anne-Sophie Armand, Sylvie Lécolle, Thierry Launay, Claude-Louis Gallien and Christophe Chanoine 

From the UMR 7060 CNRS, Equipe Biologie du développement et de la Différenciation Neuromusculaire, Centre Universitaire des Saints-Pères, Université René Descartes, F-75270 Paris Cedex 06, France

Whether the myogenic regulatory factors (MRFs) of the MyoD family can discriminate among the muscle gene targets for the proper and reproducible formation of skeletal muscle is a recurrent question. We have previously shown that, in Xenopus laevis, myogenin specifically transactivated muscle structural genes in vivo. In the present study, we used the Xenopus model to examine the role of XMyoD, XMyf5, and XMRF4 for the transactivation of the (nicotinic acetylcholine receptor) nAChR genes in vivo. During early Xenopus development, the expression patterns of nAChR subunit genes proved to be correlated with the expression patterns of the MRFs. We show that XMyf5 specifically induced the expression of the -subunit gene in cap animal assays and in endoderm cells of Xenopus embryos but was unable to activate the expression of the -subunit gene. In embryos, overexpression of a dominant-negative XMyf5 variant led to the repression of -but not -subunit gene expression. Conversely, XMyoD and XMRF4 activated -subunit gene expression but were unable to activate -subunit gene expression. Finally, all MRFs induced expression of the -subunit gene. These findings strengthen the concept that one MRF can specifically control a subset of muscle genes that cannot be activated by the other MRFs.

Received for publication, May 7, 2003 , and in revised form, May 30, 2003.

^* This work was supported in part by grants from the Association Française contre les Myopathies. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 33-1-4286-2153; Fax: 33-1-4286-2119; E-mail: chanoine{at}biomedicale.univparis5.fr.

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