Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In this study, an endogenous factor(s) involved in the suppression of the induction of CYP1A1 was studied. Analyzing the sequences, we found that the sequence of xenobiotic responsive element (XRE) in the upstream region of the human CYP1A1 gene was overlapped with that of the upstream stimulatory factor 1 (USF1)-binding site in mouse metallothionein I promoter. In fact, a gel shift assay using a specific competitor or mutant probes showed that the core sequence of human XRE was specifically recognized by USF1. The amount of USF1 in the nuclear extracts from HepG2 cells was smaller than that from rat and rabbit livers as assayed by the binding to XRE. To determine whether or not USF1 could inhibit the interaction of aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (Arnt) complex with XRE, we transfected USF1-SR alpha expression vector into HepG2 cells. The results showed that no interaction of AhR/Arnt complex with XRE occurred even when the cells were treated with 2,3,7,8-tetrachlorodibenzofuran (TCDF). Furthermore, the S1 nuclease protection assay showed that the induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) was depressed by the transfection of USF1-SR alpha into HepG2 cells. Thus, it is highly possible that USF1 negatively regulates the induction of CYP1A1 in humans.
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PMID:Upstream stimulatory factor 1 (USF1) suppresses induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) in HepG2 cells. 938 70

Unlike most experimental animals, treatment of adult rabbits with 3-methylcholanthrene (MC) does not induce the expression of the CYP1A1 gene. In this study, we show that DNA methylation plays one of the key roles in the suppression of CYP1A1 gene expression. S1 nuclease protection assay showed that the induction of CYP1A1 mRNA by MC occurred in rabbit kidney RK13 cells but not in rabbit lung R9ab cells, while aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) mRNAs were expressed in both cells at similar levels. Interestingly, the treatment of R9ab cells with a DNA demethylating agent, 5-aza-2'-deoxycitidine, resulted in the induction of the expression of the CYP1A1 gene by MC. The results indicate that DNA methylation is one of the factors involved in the loss of the MC-induced expression of the CYP1A1 gene. Thus, it seemed that the binding of the AhR/Arnt complex to the xenobiotic-responsive element (XRE) was inhibited by the hypermethylation of CpG dinucleotides within an XRE core sequence (5'-CGTG-3'). To explore this possibility, we compared the methylation status of XRE in R9ab cells with that in RK13 cells. A bisulfite sequence analysis using genomic DNAs from R9ab cells showed that the CpG site within XRE was highly methylated on both coding and non-coding strands. In contrast to this result, the hypomethylation of XRE was seen in RK13 cells. To examine whether or not the binding of the AhR/Arnt heterodimer to XRE is affected by the methylation status of XRE, a gel shift assay using a methylated XRE as a probe was carried out. As expected, the AhR/Arnt complex could not bind to the methylated XRE. From these results, we conclude that the cell type-specific transcription of the rabbit CYP1A1 gene is caused by DNA methylation.
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PMID:Silencing of CYP1A1 expression in rabbits by DNA methylation. 964 36