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 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.
Kim
Ji-Won
JW
Department of Anatomy, Ajou University, School of Medicine, Suwon, 442-749, Korea.
Seghers
Victor
V
Cho
Jang-Hyeon
JH
Kang
Yup
Y
Kim
Soyeon
S
Ryu
Yoonseok
Y
Baek
Kwanghee
K
Aguilar-Bryan
Lydia
L
Lee
Young-Don
YD
Bryan
Joseph
J
Suh-Kim
Haeyoung
H
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007340:Insulinoma; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010190:Pancreatic Neoplasms; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011401:Promoter Regions, Genetic; D051381:Rats; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; C577507:ABCC8 protein, human; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; C093970:NEUROD1 protein, human; C501008:Neurod1 protein, mouse