{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T04:10:32Z","timestamp":1700194232794},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,7,8]],"date-time":"2004-07-08T00:00:00Z","timestamp":1089244800000},"content-version":"vor","delay-in-days":189,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Potential mechanisms were investigated whereby <jats:italic>CYP2B18<\/jats:italic>, a cytochrome P450 gene exhibiting high constitutive expression but only low levels of phenobarbital\u2010inducibility in the guinea pig liver, may be differentially regulated versus the highly inducible rat <jats:italic>CYP2B2<\/jats:italic> gene. To comparatively assess potential regulatory sequences associated with <jats:italic>CYP2B18<\/jats:italic>, a guinea pig genomic library was screened enabling isolation of the <jats:italic>CYP2B18<\/jats:italic> gene. The genomic screening process resulted in the identification of at least four closely\u2010related <jats:italic>CYP2B18<\/jats:italic> genes, designated here as <jats:italic>CYP2B18A\u2010D<\/jats:italic>. Of these isolates, <jats:italic>CYP2B18A<\/jats:italic> exhibited sequence identical to that of the CYP2B18 cDNA. Further, the deduced amino acid sequence of the CYP2B18 cDNA was identical to that of N\u2010terminal and internally\u2010derived peptide sequences obtained in this investigation from CYP2B18 protein isolated from guinea pig liver. Genomic structural sequences were derived for <jats:italic>CYP2B18A<\/jats:italic>, together with the respective 5\u2032\u2010upstream and intronic regions of the gene. Comparison of the <jats:italic>CYP2B18A<\/jats:italic> and <jats:italic>CYP2B2<\/jats:italic> gene sequences revealed the lack of repetitive <jats:italic>LINE<\/jats:italic> gene sequences in <jats:italic>CYP2B18A<\/jats:italic>, putative silencing elements that effect neighboring genes, although these sequences were present in both 5\u2032\u2010upstream and 3\u2032\u2010downstream regions of <jats:italic>CYP2B2<\/jats:italic>. We determined that the phenobarbital\u2010responsive enhancer module was absent from the 5\u2032\u2010upstream region as well as the intronic regions of <jats:italic>CYP2B18A<\/jats:italic> gene. We hypothesize that the compromised phenobarbital inducibility of CYP2B18A stems from its lack of a functional phenobarbital responsive enhancer module. \u00a9 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:124\u2013130, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). 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