IAPP/amylin gene transcriptional control region: evidence for negative regulation.
Aberrant expression of the islet amyloid polypeptide (IAPP) gene might be involved in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Here, we report that IAPP promoter-luciferase constructs revealed tissue-specific activity. This activity was not mediated by cAMP. Sequential 5' deletions of the IAPP promoter caused a progressive derepression of the IAPP gene promoter in IAPP-producing cells. Comparison of the nucleotide sequence of the IAPP promoter with that of the insulin promoter (both active in pancreatic beta-cells) reveals two sequence elements of putative importance: an insulin enhancer-like sequence and an element which corresponds to a protected domain in rat insulin I gene promoter footprint experiments.
Mosselman
S
S
Institute of Molecular Biology and Medical Biotechnology, Utrecht, The Netherlands.
Höppener
J W
JW
de Wit
L
L
Soeller
W
W
Lips
C J
CJ
Jansz
H S
HS
D000682:Amyloid / Q000235:genetics*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002872:Chromosome Deletion; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000235:genetics; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016385:TATA Box; D014407:Tumor Cells, Cultured
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005576:Colforsin; D003994:Bucladesine; D008156:Luciferases