Transactivation of the mouse sulfonylurea receptor I gene by BETA2/NeuroD.

The sulfonylurea receptor 1 (SUR1) plays a key role in regulation of insulin secretion in pancreatic β-cells. In this study we investigated the mechanism for tissue-specific expression of the SUR1 gene. A −138/−20 fragment exhibited basal promoter activity while the −660/−20 fragment contained a regulatory element for tissue-specific expression of the mouse SUR1 gene. A pancreatic β-cell-specific transcription factor, BETA2 (β-cell E box transcription factor)/NeuroD, enhanced the promoter activity of the −660/−20 fragment in cooperation with E47. Coexpression of a dominant negative mutant of BETA2/NeuroD, BETA2(1–233), repressed the promoter activity of the −660/−20 fragment. BETA2/NeuroD bound specifically to the E3 element located at −141. The E3 sequence in a heterologous context conferred transactivation by BETA2/NeuroD in HeLa and HIT cells. Mutation of E3 eliminated the stimulatory effect of BETA2/NeuroD. Unlike BETA2/NeuroD, neurogenin 3 (ngn3) could not activate the E3 element in HeLa cells. Overe...