Early growth response 1 loops the CYP2B6 promoter for synergistic activation by the distal and proximal nuclear receptors CAR and HNF4alpha.

ABSTRACT: Nuclear xenobiotic receptor CAR activates transcription of the CYP2B6 gene by directly binding to the distal enhancer PB responsive enhancer module (PBREM). This CAR-mediated activation is synergized by transcription factors early growth response 1 (EGR1) and hepatocyte-enriched nuclear factor 4alpha (HNF4alpha) that bind to the proximal element OA response element KI (OARE(KI)) [Inoue, K., & Negishi, M. (2008). Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene. J. Biol. Chem. 283, 10425-10432]. Two additional EGR1 binding sites have now been found just downstream from PBREM. Internal deletion of EGR1 sites within the context of the -1.8 kb CYP2B6 promoter, which contains both PBREM and OARE(KI), revealed that the distal and proximal EGR1

SUBMITTER: Inoue K 

PROVIDER: S-EPMC3178840 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature