Identification of a functional glucocorticoid response element in the CYP3A1/IGC2 gene

DNA Cell Biol. 1998 Jan;17(1):39-49. doi: 10.1089/dna.1998.17.39.


The rat CYP3A subfamily of cytochrome P450 consists of steroid- and drug-metabolizing enzymes inducible by pregnenolone 16alpha-carbonitrile and by supra-physiological doses of dexamethasone. The induction of CYP3A by dexamethasone has been proposed to be mediated by a mechanism distinct from the glucocorticoid receptor mediated response. However, a synergistic induction of CYP3A has been observed with physiological doses of glucocorticoids and other CYP3A inducers. We have identified the presence of a glucocorticoid-responsive element in the CYP3A1/IGC2 gene that mediates the induction with physiological doses of glucocorticoids. A 219-bp dexamethasone responsive fragment of the CYP3A1/IGC2 gene localized at -2100/-1882 bp upstream of the transcription initiation site was identified in transfection experiments with HepG2 cells. Maximum induction was achieved with 50-100 nM dexamethasone. DNase I footprinting analysis revealed two glucocorticoid receptor-protected sequences in the 5' flank of the CYP3A1/IGC2 gene. Point mutations in footprint I (-1982/-1960-bp) completely abolished binding and transcription activation whereas a mutation in footprint II (-2001/-1986-bp) only decreased the binding and had no effect on transcription activation. These results led to the conclusion that the glucocorticoid response element present in footprint I mediated the dexamethasone response in transfection experiments with HepG2 cells. Pregnenolone 16alpha-carbonitrile failed to induce any transcriptional effect mediated by this response element in the HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA Footprinting
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Glucocorticoids / physiology*
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Rats
  • Receptors, Glucocorticoid / physiology
  • Sequence Deletion
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A

Associated data

  • GENBANK/X98335