Regulatory DNA elements of phenobarbital-responsive cytochrome P450 CYP2B genes.
This article reviews recent progress in characterizing cis-acting DNA elements of the phenobarbital-inducible CYP2B genes. Whereas proximal DNA elements such as the C/EBP binding site regulate basal transcription activity, phenobarbital-responsive enhancer activity is governed by the distal element (designated phenobarbital-responsive enhancer module, PBREM) residing about -2.3 kbp upstream from the transcription start site. Proximal elements are not required to enhance the phenobarbital-inducible transcription, since the PBREM can confer the inducibility to several heterologous promoters. Repression of the basal transcription by a negative element upstream of the -0.8 kbp region, however, may be necessary for the proper regulation of the CYP2B genes.
Honkakoski
P
P
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Negishi
M
M
D001410:Bacillus megaterium / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology*; D012045:Regulatory Sequences, Nucleic Acid
D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital