Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells, but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970 that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression of the human CYP1A2 gene.
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PMID:The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction. 812 57

Previously, we identified a novel human cytochrome P450 cDNA that is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and represents the first member of a new subfamily designated cytochrome P4501B1 (CYP1B1; Sutter, T. R., Tang, Y. M., Hayes, C. L., Wo, Y. P., Jabs, E. W., Li, X., Yin, H., Cody, C. W., and Greenlee, W. F. (1994) J. Biol. Chem. 269, 13092-13099). Here, we report on the isolation and initial characterization of the CYP1B1 gene. The CYP1B1 gene maps to human chromosome 2 at 2p21-22 and contains three exons and two introns. The putative open reading frame starts in the second exon and is 1629 base pairs in length. Southern analysis using DNA probes directed to each of the three exons confirmed that CYP1B1 is a single copy gene. Human CYP1B1 differs from its two most closely related members of the cytochrome P450 superfamily, CYP1A1 and CYP1A2, in the number of exons (3 versus 7) and chromosome location (2 versus 15). A single transcription initiation site was identified by primer extension analysis and S1 nuclease mapping. Based on nucleotide sequence analysis, the CYP1B1 gene lacks a consensus TATA box in the promoter region and contains nine TCDD-responsive enhancer core binding motifs (5'-GCGTG-3') located within a 2.5-kilobase pair genomic fragment 5'-ward of the transcription initiation start site. Deletion analysis of chloramphenicol acetyltransferase reporter gene constructs containing 5' CYP1B1 genomic fragments indicates that a region from -1022 to -835 containing three of the nine core binding motifs contributes to the TCDD-inducible expression of CYP1B1.
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PMID:Isolation and characterization of the human cytochrome P450 CYP1B1 gene. 891 Apr 54

We have previously demonstrated that H2O2 downregulates CYP1A1 and CYP1A2 transcription in isolated rat hepatocytes (C. W. Barker, et al., 1994, J. Biol. Chem. 269, 3985-3990). In the present study, induction of chloramphenicol acetyltransferase (CAT) expression driven by 3.1 kb of rat CYP1A1 upstream regulatory sequences was suppressed by 56% in Hepa-1 cells treated with H2O2. Similarly, H2O2 inhibited CAT expression from vectors containing two copies of either xenobiotic-response element (XRE) 1 or XRE2. H2O2 did not inhibit basal CAT expression in cells that were not treated with the inducer beta-napthoflavone. Electrophoretic mobility shift assays demonstrated that the suppression of XRE-dependent transcription by H2O2 was not due to changes in nuclear aryl hydrocarbon (Ah) receptor DNA binding activity. Several types of experiments indicated that modulation of XRE enhancer strength by various means could modify H2O2-dependent suppression of CAT expression. Conditions that increased the transactivation potential of the Ah receptor (increase in XRE copy number or shortening of the distance between XREs and the minimal CYP1A1 promoter) attenuated the action of H2O2, while conditions that reduced XRE-mediated transactivation potential (decrease in XRE copy number, increase of the distance between the XRE and the promoter, or reduction of the number of bound Ah receptors by lowering the concentration of inducer) potentiated the inhibitory action of H2O2.
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PMID:Suppression of CYP1A1 transcription by H2O2 is mediated by xenobiotic-response element. 970 4