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Glucagon gene expression is negatively regulated by hepatocyte nuclear factor 3 beta
J Philippe1, C Morel, V R Prezioso
1Department of Genetics & Microbiology, Centre Médical Universitaire, Geneva, Switzerland.
Molecular and Cellular Biology
|May 1, 1994
Summary
Hepatocyte nuclear factor 3 beta (HNF-3 beta) represses rat glucagon gene expression by binding to the G2 enhancer. This finding suggests a role for HNF-3 beta in islet cell development and glucagon regulation.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- Pancreatic glucagon gene expression is regulated by transcription factors binding to specific DNA control elements.
- The G2 sequence is a major enhancer of the rat glucagon gene, interacting with protein complexes.
Purpose of the Study:
- To identify protein complexes interacting with the G2 enhancer.
- To elucidate the role of these complexes in regulating glucagon gene transcription.
Main Methods:
- Protein complex binding assays using mutant G2 sequences.
- Mutational analyses of the G2 enhancer.
- Cotransfection assays with HNF-3 beta cDNA and reporter genes in glucagon-producing cells.
Main Results:
- The G2 enhancer interacts with three protein complexes: A1, A2, and A3.
- A2 is islet cell-specific and crucial for transcriptional activity.
- Hepatocyte nuclear factor 3 beta (HNF-3 beta) was identified as complex A1.
- HNF-3 beta binds to a site overlapping A2 and represses glucagon gene expression.
Conclusions:
- HNF-3 beta plays a repressive role in regulating rat glucagon gene expression.
- The findings support the hypothesis of an endodermal origin for islet cells.
- HNF-3 beta is implicated in the control of glucagon gene expression.