Interaction of Maf transcription factors with Pax-6 results in synergisticactivation of the glucagon promoter

In the endocrine pancreas, a-cell-specific expression of the glucagon gene is mediated by DNA-binding proteins that interact with the G1 proximal prom oter element. Among these proteins, the paired domain transcription factor Pax-6 has been shown to bind to G1 and to transactivate glucagon gene expre ssion. Close to the Pax-6-binding site, we observed the presence of a bindi ng 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 transa ctivating effect on the glucagon promoter was greatly enhanced by the simul taneous 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 GI element. Furthermore, we found that Maf enhanced the Pax-6 DNA bi nding capacity. Our data indicate that Maf transcription factors may contri bute to glucagon gene expression in the pancreas.