Negative regulation of human insulin gene expression by the 5'-flanking region in non-pancreatic cells.
We have examined the effect of the 5'-flanking region of the human insulin gene on its expression in non-pancreatic cells. The presence of the region containing the insulin gene enhancer (-339 to -169 bp) markedly repressed the promoter activity of the insulin gene. This suppressive phenomenon was restored by the addition of forskolin or dibutyryl cAMP, suggesting that this region alone is not sufficient to repress completely insulin gene expression in the presence of extracellular stimuli which increase the intracellular cAMP level. The hypervariable region (HVR) located at -365 bp also repressed the promoter activity. These results show negative regulation of human insulin gene expression in non-pancreatic cells by these regions.
Takeda
J
J
Second Department of Internal Medicine, Kyoto University School of Medicine, Japan.
Ishii
S
S
Seino
Y
Y
Imamoto
F
F
Imura
H
H
D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D015342:DNA Probes; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007668:Kidney; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D007328:Insulin; D005576:Colforsin; D003994:Bucladesine; D015500:Chloramphenicol O-Acetyltransferase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate