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J. Biol. Chem., Vol. 279, Issue 53, 55651-55658, December 31, 2004

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Characterization of a Cardiac-specific Enhancer, Which Directs -Cardiac Actin Gene Transcription in the Mouse Adult Heart^*

Marguerite Lemonnier and Margaret E. Buckingham

From the CNRS URA 2578, Département de Biologie du Développement, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France

Expression of the mouse -cardiac actin gene in skeletal and cardiac muscle is regulated by enhancers lying 5' to the proximal promoter. Here we report the characterization of a cardiac-specific enhancer located within -2.354/-1.36 kbp of the gene, which is active in cardiocytes but not in C2 skeletal muscle cells. In vivo it directs reporter gene expression to the adult heart, where the proximal promoter alone is inactive. An 85-bp region within the enhancer is highly conserved between human and mouse and contains a central AT-rich site, which is essential for enhancer activity. This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These results are discussed in the context of MEF2 activity and of the regulation of the -cardiac actin locus.

Received for publication, September 27, 2004

^* This work was supported by the Pasteur Institute and the CNRS. 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.

An INSERM research scientist.

To whom correspondence should be addressed. Tel.: 33-1-45-68-8477; Fax: 33-1-40-61-3452; E-mail: margab{at}pasteur.fr.

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