The CYP2B2 phenobarbital response unit contains an accessory factor element and a putative glucocorticoid response element essential for conferring maximal phenobarbital responsiveness.

The Journal of Biological Chemistry
C StoltzAlan Anderson

Abstract

Hepatic cytochrome P450s play a critical role in the metabolism of hydrophobic xenobiotics. One of the major unsolved problems in xenobiotic metabolism is the molecular mechanism whereby phenobarbital induces hepatic enzymes, particularly CYP2B1 and CYP2B2 in rat liver. By using primary rat hepatocytes for transfection analyses, we previously identified in the CYP2B2 5'-flank a 163-base pair Sau3AI fragment that confers phenobarbital inducibility on a cat reporter gene and that has the properties of a transcriptional enhancer. Transfection experiments with sub-regions of the Sau3AI fragment now indicate that a central core together with an upstream or downstream accessory element within the fragment can confer phenobarbital responsiveness. One such accessory element, AF1, was identified and localized. DNase I footprinting analysis revealed the presence of a footprint overlapping this AF1 element. It also identified three other major protected regions, two of which are putative recognition sites for known transcription factors. Site-directed mutagenesis indicated that a putative glucocorticoid response element as well as a nuclear factor 1 site and an associated nuclear receptor hexamer half-site are essential for conferring max...Continue Reading

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Citations

Oct 13, 2001·Biochemical Pharmacology·K A SchoedelR F Tyndale
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·T Sueyoshi, M Negishi
Oct 12, 2000·Biochemical and Biophysical Research Communications·H YamadaK Oguri
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Sep 11, 2008·Biochemical Pharmacology·Etienne Audet-WalshAlan Anderson
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