CHARACTERIZATION OF THE MOUSE HNF-4 GENE AND ITS EXPRESSION DURING MOUSE EMBRYOGENESIS

Hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear recepto r gene superfamily with unknown ligand. It has been assumed to play an important role in the regulation of gene expression in the liver. Her e, we report the cloning and characterization of the mouse HNF-4 gene, as well as its expression during embryogenesis. The HNF-4 protein is encoded by ten exons. The gene structure is unique in the steroid rece ptor superfamily in that the second zinc finger is encoded by two exon s. HNF-4 mRNA is expressed in a limited number of mouse adult tissues: liver, kidney, intestine, stomach and skin. HNF-4 could play an impor tant role in the formation and function of visceral yolk sac and in th e development of the liver and kidney since its mRNA, as determined by in situ hybridization, appears upon primary differentiation of these organs. As a first step in the study of the regulatory elements of the HNF-4 gene, we mapped the transcription start site and carried out DN ase I hypersensitive site (HS) analysis over a region of approximately 22kb upstream of the gene. The complexity of the HSs suggests that mu ltiple elements might contribute to the transcriptional regulation of the HNF-4 gene.