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

@entity3420 @entity7570 @entity134 @entity619 @entity22097 @entity12531 @entity35
The @entity35 @entity12531 subfamily of cytochrome P450 consists of @entity134 - and drug-metabolizing enzymes inducible by @entity22097 and by supra-physiological doses of @entity619 . The induction of @entity12531 by @entity619 has been proposed to be mediated by a mechanism distinct from the glucocorticoid receptor mediated response. However, a synergistic induction of @entity12531 has been observed with physiological doses of glucocorticoids and other @entity12531 inducers. We have identified the presence of a glucocorticoid-responsive element in the @entity7570 /IGC2 gene that mediates the induction with physiological doses of glucocorticoids. A 219-bp @entity619 responsive fragment of the @entity7570 /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 @entity619 . @entity3420 footprinting analysis revealed two glucocorticoid receptor-protected sequences in the 5' flank of the @entity7570 /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 @entity619 response in transfection experiments with HepG2 cells. @entity22097 failed to induce any transcriptional effect mediated by this response element in the HepG2 cells.
