Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily

Abstract

The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5' flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 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-supported activity in non-liver cells.