1999 Volume 14 Issue supplement Pages 88-89
A CYP3A1 gene, which encodes testosterone 613-hydroxylase in rats, is isolated and analyzed. This gene encodes an active P450 form also corresponding to CYP3A23 1). The promoter region of CYP3A1 gene contains three binding sites (A, B and C site) for liver nuclear proteins similar to CYP3A2 gene1, 2). Both CYP3A1 and CYP3A2 genes are transactivated by HNF-4 through A sites, in COS-1 cells co-transfected with a HNF-4 expression vector3). The HNF-4-mediated activation of CYP3A1 gene is suppressed by ARP-1 and/or EAR-3 through B site without competition with HNF-4. The B site is known as a binding site for PXR-RXR heterodimer4). The PXR-RXR binding site also exist in CYP3A4 genes5) but its position differs from that of CYP3A1 gene. The homology of the 5' region from -1 by to -180 by is low between two genes. A CYP3A4-reporter fused gene is not activated in the presence of inducer, rifampicin, in HepG2 cells, which expresses native HNF-4 and PXR, although the CYP3A4-reporter fused gene is activated by ARP-1 and/or EAR-3. These results suggest, in addition to PXR response, that the different induction profile CYP3A1 and CYP3A4 may be arisen from species-specific transcriptional regulation by nuclear factors.
