Transcriptional Regulation of Cytochrome P450 Genes

AbstractThe discovery and characterization of nuclear receptors, such as the aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR), and their involvement in the transcriptional regulation of cytochrome P450s have greatly increased our understanding of this process while providing a mechanistic basis for additional levels of control. This chapter details the role of AHR, CAR, and PXR in controlling cytochrome P450 expression, including cross talk between the receptors, the different classes of ligands bound by the receptors and the responses that they elicit, polymorphisms and splice variants of CAR and PXR, and species specificity in the context of CAR and PXR. Each of these factors and the interplay between them contribute to the growing layers of complexity that are being uncovered with regard to the transcriptional regulation of cytochrome P450 genes. The potential contributions of humanized transgenic models to this field are also discussed.