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The FASEB Journal, Vol 10, 809-818, Copyright © 1996 by The Federation of American Societies for Experimental Biology

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Cytochromes P450 5: induction of cytochrome P4501A1: a model for analyzing mammalian gene transcription

JP Whitlock Jr, ST Okino, L Dong, HP Ko, R Clarke-Katzenberg, Q Ma and H Li
Department of Molecular Pharmacology, Stanford University of Medicine, California 94305-5332, USA.

The induction of microsomal cytochrome P4501A1 by polycyclic aromatic hydrocarbons represents an interesting response by which mammalian cells adapt to xenobiotic exposure. Enzyme induction reflects increased transcription of the corresponding CYP1A1 gene. Analyses of the induction mechanism using genetic, biochemical, and molecular biological approaches have revealed a novel transcriptional regulatory pathway that involves ligand-dependent heterodimerization between two basic helix-loop-helix proteins (the Ah receptor and Arnt), interaction of the heterodimer with a xenobiotic-responsive enhancer, transmission of the induction signal from the enhancer to the CYP1A1 promoter, and alterations in chromatin structure. Current techniques permit examination of the induction mechanism in intact cells and analyses of the CYP1A1 gene in its native chromosomal configuration. Such experiments generate new insights into the control of mammalian transcription that are of relatively broad interest.


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Copyright © 1996 by The Federation of American Societies for Experimental Biology.