MafA is a dedicated activator of the insulin gene in vivo.

Artner I, Hang Y, Guo M, Gu G, Stein R
J Endocrinol. 2008 198 (2): 271-9

PMID: 18515495 · PMCID: PMC3787904 · DOI:10.1677/JOE-08-0063

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.

MeSH Terms (20)

Animals Basic Helix-Loop-Helix Transcription Factors Chick Embryo DNA Electroporation Endoderm Glucagon HeLa Cells Humans Immunohistochemistry Insulin Islets of Langerhans MafB Transcription Factor Maf Transcription Factors Mice Nerve Tissue Proteins Promoter Regions, Genetic Protein Binding Protein Multimerization Reverse Transcriptase Polymerase Chain Reaction

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