TRANSACTIVATION OF THE RAT CYP2C13 GENE PROMOTER INVOLVES HNF-1, HNF-3, AND MEMBERS OF THE ORPHAN RECEPTOR SUBFAMILY

The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addit ion to being developmentally regulated, the expression of 2C13 is rest ricted to the liver and suppressed by the female pattern of growth hor mone (GH) secretion at the transcriptional initiation level. In this s tudy, we show that the liver-specific expression, but not the regulati on by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5' flank. T ransactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcrip tion factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C 13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-su pported activity in non-liver cells.