Enhancer elements in the mouse Cyp1a2 gene for constitutive expression

CYP1A2 is one of the major hepatic cytochrome P450s that is involved in the metabolism of many drugs, as well as in the activation of chemical carcinogens. To elucidate the transcriptional regulation of the constitutive expression of the mouse Cypla2 gene, the 4.8-kbp 5(')-flanking region of th...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-10, Vol.297 (5), p.1297
Main Authors: Uchida, Yo-ichi, Yano, Aiko, Kumakura, Shin-ichi, Sakuma, Tsutomu, Nemoto, Nobuo
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Nucleus - metabolism
Cells, Cultured
Cloning, Molecular
Cytochrome P-450 CYP1A2 - biosynthesis
Cytochrome P-450 CYP1A2 - genetics
Enhancer Elements, Genetic
Liver - enzymology
Luciferases - metabolism
Male
Mice
Mice, Inbred C57BL
Models, Genetic
Molecular Sequence Data
Mutation
Protein Binding
Transcription, Genetic
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Summary:CYP1A2 is one of the major hepatic cytochrome P450s that is involved in the metabolism of many drugs, as well as in the activation of chemical carcinogens. To elucidate the transcriptional regulation of the constitutive expression of the mouse Cypla2 gene, the 4.8-kbp 5(')-flanking region of the gene was analyzed for transcriptional activity using a primary cultured mouse hepatocyte system. With 5(')- and 3(')-deletion analysis, two enhancer elements, i.e., a 20-bp DNA fragment (E1) from -4401 to -4382 and a 9-bp (E2) from -4300 to -4292, were identified. E1 and E2 contain a phorbol 12-O-tetradecanoate-13-acetate (TPA)-responsive element (TRE) and TRE-like element, respectively. Electrophoretic mobility shift assay confirmed specific binding between these two enhancer elements and nuclear proteins. Site-directed mutagenesis assay suggested that the TRE element in E1 is essential for constitutive expression of the mouse Cypla2 gene.
ISSN:0006-291X