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

Kim, JW; Seghers, V; Cho, JH; Kang, Y; Kim, S; Ryu, Y; Baek, K; Aguilar-Bryan, L; Lee, YD; Bryan, J; Suh-Kim, H
Molecular endocrinology (Baltimore, Md.), 16(5):1097-1107, 2002
Journal Title
Molecular endocrinology (Baltimore, Md.)
The sulfonylurea receptor 1 (SUR1) plays a key role in regulation of insulin secretion in pancreatic beta-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 beta-cell-specific transcription factor, BETA2 (beta-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.
MeSH terms
*ATP-Binding Cassette TransportersAnimalsBase SequenceBasic Helix-Loop-Helix Transcription FactorsBinding SitesDNA-Binding Proteins/metabolism/*pharmacologyGene ExpressionHela CellsHumansInsulinomaMiceMolecular Sequence DataMutagenesisPancreatic NeoplasmsPeptide Fragments/genetics/metabolismPotassium Channels/*genetics/metabolism*Potassium Channels, Inwardly RectifyingPromoter Regions, GeneticRatsReceptors, Drug/*genetics/metabolismRegulatory Sequences, Nucleic AcidReverse Transcriptase Polymerase Chain ReactionTrans-Activators/metabolism/*pharmacology*Transcriptional ActivationTransfectionTumor Cells, Cultured
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
강, 엽이, 영돈서, 해영
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