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Hepatocyte nuclear factor 1 negatively regulates amylin gene expression
Janelle Green1, Dorit Naot, Garth Cooper
1M.E. Müller-Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. janelle.green@unibas.ch
Biochemical and Biophysical Research Communications
|October 3, 2003
Summary
Hepatocyte nuclear factor 1 (HNF1) negatively regulates amylin gene expression. This finding in maturity-onset diabetes of the young (MODY) may explain how HNF1 mutations contribute to diabetes development.
Area of Science:
- Molecular Biology
- Genetics
- Endocrinology
Background:
- Maturity-onset diabetes of the young (MODY) is a monogenic diabetes subtype.
- Hepatocyte nuclear factor 1 (HNF1), encoded by the MODY3 gene, binds the insulin promoter.
- Pancreatic gene promoters for insulin, glucokinase, and amylin bind similar transcription factors.
Purpose of the Study:
- To investigate if HNF1 regulates amylin gene expression.
- To elucidate the role of HNF1 in glucose homeostasis and diabetes.
Main Methods:
- Electrophoretic mobility shift assay (EMSA) to detect HNF1 binding to the amylin promoter.
- Co-transfection assays using HNF1 expression vector and amylin-CAT reporter plasmid.
Main Results:
- HNF1 specifically binds to the amylin promoter.
- Amylin promoter activity decreased by 85% upon co-transfection with HNF1 expression vector.
- Demonstrated negative regulation of amylin gene expression by HNF1.
Conclusions:
- HNF1 transcription factor negatively regulates amylin gene expression.
- This regulatory mechanism may partially explain diabetes development in HNF1 mutations associated with MODY.