INVOLVEMENT OF HNF-1 IN THE REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-EXPRESSION IN THE KIDNEY

The cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK) gene is differentially expressed in several tissues, A specific set of regulatory elements in the promoter are responsible for the control o f PEPCK gene transcription and, in turn, determine its distinct metabo lic role in each tissue, DNase I footprinting analysis of the PEPCK pr omoter, using nuclear proteins from tissues which express the gene for PEPCK, and transient expression assays in renal cell lines have demon strated that the HNF-1 recognition motif (P2) in the PEPCK promoter ch aracterizes kidney-specific expression. This site is required also for the response to acidosis. Since the PZ site is not involved in the ex pression of the PEPCK gene in the liver, we propose that its critical role in the kidney stems from a combination of abundance of HNF-1 toge ther with low concentrations of members of the C/EBP family in this ti ssue. (C) 1997 Federation of European Biochemical Societies.