The -4 kilobase promoter region of the winged helix transcription factor HNF-3α gene elicits transgene expression in mouse embryonic hepatic and intestinal diverticula

Abstract

Murine hepatocyte nuclear factor-3α (HNF-3α) protein is a member of a large family of developmentally regulated transcription factors that share homology in the winged helix/fork headDNA binding domain and participate in embryonic pattern formation. HNF-3α also mediates 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 HNF-3α gene were sufficient to elicit hepatoma-specific expression in transfection assays and reported on a novel HNF-3α expression pattern in the renal pelvis urothelium of the embryonic and adult kidney. We also showed that retinoic acid mediated activation of the HNF-3α gene required -4 kb of the HNF-3α promoter region in F9 teratocarcinoma transfections. In order to determine regulatory sequences mediating the HNF-3α cellular expression pattern in developing mouse embryos, we created transgenic mice bearing the -4 kb HNF-3α promoter region driving expression of the β-galactosidase transgene. Embryonic analysis of two transgenic mouse lines demonstrated that the -4 kb HNF-3α promoter sequences were sufficient to elicit transgene expression in the developing liver, intestine, esophagus, nasal epithelial cells and floorplate of the neurotube, but not in the mesodermal notochord or in the lung bud. One of the transgenic lines also exhibited proper expression in the mesonephric ducts and metanephric diverticulum, suggesting that the -4 kb HNF-3α promoter region contained a subset of the regulatory sequences necessary for HNF-3α expression in the developing kidney.