| First Author | Artner I | Year | 2008 |
| Journal | J Endocrinol | Volume | 198 |
| Issue | 2 | Pages | 271-9 |
| PubMed ID | 18515495 | Mgi Jnum | J:138415 |
| Mgi Id | MGI:3805137 | Doi | 10.1677/JOE-08-0063 |
| Citation | Artner I, et al. (2008) MafA is a dedicated activator of the insulin gene in vivo. J Endocrinol 198(2):271-9 |
| abstractText | 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 MafB in glucagon+alpha-cells. MafB-/- animals are also deficient in insulin+ and glucagon+ cell production during embryogenesis. However, only MafA over-expression 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 assay. 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 on 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. |
