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Originally published In Press as doi:10.1074/jbc.M104523200 on July 16, 2001

J. Biol. Chem., Vol. 276, Issue 38, 35751-35760, September 21, 2001
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Interaction of Maf Transcription Factors with Pax-6 Results in Synergistic Activation of the Glucagon Promoter*

Nathalie Planque, Laurence Leconte, Frédéric M. Coquelle, Sofia Benkhelifa, Patrick Martin, Marie-Paule Felder-Schmittbuhl, and Simon SauleDagger

From the CNRS-UMR 146, Institut Curie-Section de Recherche, Bât 110, Centre Universitaire, 91405 Orsay, France

In the endocrine pancreas, alpha -cell-specific expression of the glucagon gene is mediated by DNA-binding proteins that interact with the G1 proximal promoter element. Among these proteins, the paired domain transcription factor Pax-6 has been shown to bind to G1 and to transactivate glucagon gene expression. Close to the Pax-6-binding site, we observed the presence of a binding site for a basic leucine zipper transcription factor of the Maf family. In the present study, we demonstrate the presence of Maf family members in the endocrine pancreas that bind to G1 and transactivate glucagon promoter expression. In transient transfection experiments, we found that the transactivating effect on the glucagon promoter was greatly enhanced by the simultaneous expression of Maf transcription factors and Pax-6. This enhancement on glucagon transactivation could be correlated with the ability of these proteins to interact together but does not require binding of Maf proteins to the G1 element. Furthermore, we found that Maf enhanced the Pax-6 DNA binding capacity. Our data indicate that Maf transcription factors may contribute to glucagon gene expression in the pancreas.

* This work was supported by grants from the CNRS, the Institut Curie, the Association Retina France, the Association pour la Recherche Contre le Cancer, the Ligue Nationale Contre le Cancer, and L'Association de Secours Des Amis des Sciences.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.

Dagger To whom correspondence should be addressed. Tel.: 33 1 69 86 71 53; Fax: 33 1 69 07 45 25; E-mail: Simon.Saule@curie.u-psud.fr.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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