Transactivation of the Mouse Sulfonylurea Receptor I Gene by BETA2/NeuroD

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 16; no. 5; pp. 1097 - 1107
• Main Authors: Kim, Ji-Won, Seghers, Victor, Cho, Jang-Hyeon, Kang, Yup, Kim, Soyeon, Ryu, Yoonseok, Baek, Kwanghee, Aguilar-Bryan, Lydia, Lee, Young-Don, Bryan, Joseph, Suh-Kim, Haeyoung
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01.05.2002; Oxford University Press
• DOI: 10.1210/mend.16.5.0934
• ISSN: 0888-8809

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. Overexpression of ngn3 concomitantly increased expression of BETA2/NeuroD and SUR1 in HIT cells but not in HeLa cells. These results indicate that BETA2/NeuroD induces tissue-specific expression of the SUR1 gene through the E3 element. These results also suggest that E3 is specific for BETA2/NeuroD, and the stimulatory effect of ngn3 in HIT cells may require factors specifically expressed in HIT cells.