Hepatocyte nuclear factor 1 negatively regulates amylin gene expression.
Maturity-onset diabetes of the young (MODY) is a monogenic subtype of Type 2 diabetes, defined as having an early age of onset, with a dominant inheritance pattern. Hepatocyte nuclear factor 1 (HNF1), which is encoded by the MODY3 gene, has been shown to bind the insulin promoter. Since the promoters of three pancreas-specific genes involved in glucose homeostasis-insulin, glucokinase, and amylin bind similar transcription factors, we were interested in whether HNF1 could also regulate amylin expression. In the present study, we used the electrophoretic mobility shift assay, to demonstrate that the HNF1 transcription factor can specifically bind to the amylin promoter. Moreover, co-transfection of an HNF1 expression vector with an amylin-CAT reporter plasmid decreased the activity of the amylin promoter by 85%. These data support the hypothesis that the amylin gene is regulated by HNF1 in a negative manner and may explain partially how HNF1 mutations result in diabetes.
Green
Janelle
J
M.E. Müller-Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. janelle.green@unibas.ch
Naot
Dorit
D
Cooper
Garth
G
D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D058228:Islet Amyloid Polypeptide; D009687:Nuclear Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
D000682:Amyloid; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D058228:Islet Amyloid Polypeptide; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta