Gene structure and promoter analysis of the rat constitutive CYP2C23 gene

The CYP2C23 gene is expressed constitutively in the rat liver and kidney. It exhibits different profiles of expression in the two tissues, suggesting that several regulation processes could exist. In this paper, we report the structure of the 5'-flanking region of the CYP2C23 gene; 4.5 kbp were sequenced and analyzed. The CYP2C23 gene is present as a single copy into the rat genome and an unique transcription start site is used in both liver and kidney. Four DNase I hypersensitive sites have been mapped to the distal part of the hepatic promoter and three are detected in the kidney: only one site is present in the two tissues (L3/K1). In the proximal region, one site is specific for the kidney and one is detected in all the tissues tested. Footprint experiments allowed precise identification of the sequence of protected regions: HNF4 and CREB binding motifs are present in the distal liver-specific sites, motifs for AP-1, NF-1, and XRE-Bf are in the distal kidney site, and a Tf-LF1 binding site is localized in the L3/K1 protected site. In the proximal region, a sequence protected in all tissues contains a SP1/NF kappa B motif, whereas a sequence containing a HNF-4 binding motif is exclusively protected by kidney nuclear extracts. Altogether, the data clearly demonstrate that trans-acting factors involved in CYP2C23 gene expression differ in liver and kidney.