The CYP2B2 5' flank contains a complex glucocorticoid response unit.
Rat CYP2B1 and CYP2B2 and mouse CYP2B10 are dramatically induced by phenobarbital (PB) in liver. PB responsiveness requires the constitutive androstane receptor (CAR). However, dexamethasone treatment can also induce CYP2B genes in both rat and mouse liver. Three regions have been shown to be involved in conferring dexamethasone responsiveness on CYP2B2 reporter constructs. They are the PB response unit, a functional glucocorticoid response element at -1.3kb in the 5' flank and a weak element in the basal promoter. We report here the identification, by deletion analysis of the CYP2B2 5' flank, of new glucocorticoid response elements or accessory factor sites. Moreover, we show that CAR acts as an accessory factor in the dexamethasone response in vivo of CYP2B10 protein in mice, by increasing both the basal and induced levels. We propose a model to explain the dexamethasone responsiveness of the CYP2B2 gene in which induction is mediated by a complex glucocorticoid response unit.
Audet-Walsh
Etienne
E
Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, CHUQ, Québec, Canada.
Lachaud
Antoine Amaury
AA
Anderson
Alan
A
D024506:5' Flanking Region / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D049410:Luciferases, Renilla; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D020218:Response Elements / Q000187:drug effects / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000096:biosynthesis / Q000235:genetics*
D005938:Glucocorticoids; D003907:Dexamethasone; D049410:Luciferases, Renilla; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase