A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver
Open Access
- 24 July 2001
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 98 (16), 9116-9121
- https://doi.org/10.1073/pnas.161284298
Abstract
Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.Keywords
This publication has 31 references indexed in Scilit:
- WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse orthologEuropean Journal of Human Genetics, 2000
- Characterization and Purification of Carbohydrate Response Element-Binding Protein of the Rat L-Type Pyruvate Kinase Gene PromoterBiochemical and Biophysical Research Communications, 1999
- Overweight prevalence among youth in the United States: Why so many different numbers?International Journal of Obesity, 1999
- REGULATION OF THE EXPRESSION OF LIPOGENIC ENZYME GENES BY CARBOHYDRATEAnnual Review of Nutrition, 1997
- Expression of liver type pyruvate kinase in insulinoma cells: Involvement of LF-B1 (HNF1)Biochemical and Biophysical Research Communications, 1991
- A Simplified Method for the Preparation of Transcriptionally Active Liver Nuclear ExtractsDNA and Cell Biology, 1990
- Dietary Regulation of Gene Expression: Enzymes Involved in Carbohydrate and Lipid MetabolismAnnual Review of Nutrition, 1987
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- HIGH-YIELD PREPARATION OF ISOLATED RAT LIVER PARENCHYMAL CELLSThe Journal of cell biology, 1969