THE -4 KILOBASE PROMOTER REGION OF THE WINGED HELIX TRANSCRIPTION FACTOR HNF-3-ALPHA GENE ELICITS TRANSGENE EXPRESSION IN MOUSE EMBRYONIC HEPATIC AND INTESTINAL DIVERTICULA

Murine hepatocyte nuclear factor-3 alpha (HNF-3 alpha) protein is a me mber of a large family of developmentally regulated transcription fact ors that share homology in the winged helix/fork headDNA binding domai n and participate in embryonic pattern formation. HNF-3 alpha also med iates cell-specific transcription of genes important for the function of hepatocytes, intestinal, pancreatic and bronchiolar epithelium. We have previously determined that -520 nucleotides upstream of the rat H NF-3 alpha gene were sufficient to elicit hepatoma-specific expression in transfection assays and reported on a novel HNF-3 alpha expression pattern in the renal pelvis urothelium of the embryonic and adult kid ney. We also showed that retinoic acid mediated activation of the HNF- 3 alpha gene required -4 kb of the HNF-3 alpha promoter region in F9 t eratocarcinoma transfections. In order to determine regulatory sequenc es mediating the HNF-3 alpha cellular expression pattern in developing mouse embryos, we created transgenic mice bearing the -4 kb HNF-3 alp ha promoter region driving expression of the beta-galactosidase transg ene. Embryonic analysis of two transgenic mouse lines demonstrated tha t the -4 kb HNF-3 alpha promoter sequences were sufficient to elicit t ransgene expression in the developing liver, intestine, esophagus, nas al epithelial cells and floorplate of the neurotube, but not in the me sodermal notochord or in the lung bud. One of the transgenic lines als o exhibited proper expression in the mesonephric ducts and metanephric diverticulum, suggesting that the -4 kb HNF-3 alpha promoter region c ontained a subset of the regulatory sequences necessary for HNF-3 alph a expression in the developing kidney.