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

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MaFA is a dedicated activator of the insulin gene in vivo. / Artner, Isabella; Hang, Yan; Guo, Min; Gu, Guoqiang; Stein, Roland.

I: Journal of Endocrinology, Vol. May 30, 2008, s. 271-279.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Artner, Isabella ; Hang, Yan ; Guo, Min ; Gu, Guoqiang ; Stein, Roland. / MaFA is a dedicated activator of the insulin gene in vivo. I: Journal of Endocrinology. 2008 ; Vol. May 30. s. 271-279.

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TY - JOUR

T1 - MaFA is a dedicated activator of the insulin gene in vivo.

AU - Artner, Isabella

AU - Hang, Yan

AU - Guo, Min

AU - Gu, Guoqiang

AU - Stein, Roland

PY - 2008

Y1 - 2008

N2 - 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 MafA is only 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 if 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.

AB - 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 MafA is only 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 if 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.

U2 - 10.1677/JOE-08-0063

DO - 10.1677/JOE-08-0063

M3 - Article

VL - May 30

SP - 271

EP - 279

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 1479-6805

ER -