MafA is a dedicated activator of the insulin gene in vivo

As successful generation of insulin-producing cells could be used for diabetes treatment, a concerted effort is being made to understand the Molecular programs underlying islet beta-cell formation and function. The closely related MafA and MafB transcription factors are both key mammalian beta-cell regulators. MafA and MafB are co-expressed in insulin(+) beta-cells during embryogenesis, while in the adult pancreas only MafA is produced in beta-cells and MAB in glucagon (+) alpha-cells. MafB(-/-) animals are also deficient in insulin and glucagon(+) Cell production during embryogenesis. However, only MaFA overexpression selectively induced endogenous Insulin mRNA production in cell line-based assays, while MafB specifically promoted Glucagon expression. Here, we analyzed whether these factors were sufficient to induce insulin(+) and/or glucagon(+) cell formation within embryonic endoderm using the chick in ovo electroporation assays Ectopic expression of MaFA, but not MafB, promoted Insulin production; however, neither MafA nor MafB were capable of inducing Glucagon. Co-electroporation of MaFA with the Ngn3 transcription factor resulted in the development of more organized Cell Clusters containing both insulin- and glucagon-producing cells. Analysis of chimeric proteins of MafA and MafB demonstrated that chick Insulin activation depended oil sequences Within the MaFA C-terminal DNA-binding domain. MafA was also bound to Insulin and Glucagon transcriptional control sequences in mouse embryonic pancreas and beta-cell lines. Collectively, these results demonstrate a unique ability for MafA to independently activate Insulin transcription.