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A dioxin-responsive enhancer 3' of the human CYP1A2 gene.

A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Research Abstract Details 

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  • A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Abstract Text:

    steven t okinoSteven T Okino,linda c quattrochiLinda C Quattrochi,deepa pookotDeepa Pookot,mieko iwahashiMieko Iwahashi,rajvir dahiyaRajvir Dahiya,steven t okinoSteven T Okino,linda c quattrochiLinda C Quattrochi,deepa pookotDeepa Pookot,mieko iwahashiMieko Iwahashi,rajvir dahiyaRajvir Dahiya,

    The human CYP1A genes CYP1A1 and CYP1A2 are in a head-to-head orientation on chromosome 15. Both CYP1A genes and CYP1B1 are transcriptionally induced by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that binds 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Although the TCDD-responsive enhancers for CYP1A1 and CYP1B1 are well characterized, a similar CYP1A2 enhancer has not been identified. In the human prostate cell line RWPE-1, CYP1A2 mRNA expression is dramatically induced by TCDD. Therefore, analysis of the native CYP1A2 gene in these cells can provide insight into its induction mechanism. To identify sites that may bind AhR on the CYP1A locus, we scanned 75 kilobases of chromosome 15 sequence for high-affinity AhR binding sites. We then analyzed most of the sites for TCDD-inducible AhR interaction by chromatin immunoprecipitation. As expected, the CYP1A1 and CYP1B1 enhancers bind AhR in TCDD-treated cells. It is noteworthy that we identify a region 3' of CYP1A2 that also binds AhR in response to TCDD. We cannot detect AhR binding at other sites on the CYP1A locus. In vivo footprinting demonstrates that two AhR binding sites in the CYP1A2 3' region are occupied in TCDD-treated cells. Reporter-gene studies show that these sites confer TCDD-responsiveness to a heterologous promoter. AhR also binds to the CYP1A2 3' region in TCDD-treated LS180 cells but not in HepG2 and ND-1 cells. In the latter cell lines, the CYP1A2 3' region is extensively methylated. In summary, we identify a novel TCDD-responsive enhancer for CYP1A2. We were surprised to find that this enhancer is not conserved across species and is primarily human-specific.

    A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Publishing Authors By Initials

    st okinoST Okino,lc quattrochiLC Quattrochi,d pookotD Pookot,m iwahashiM Iwahashi,r dahiyaR Dahiya,st okinoST Okino,lc quattrochiLC Quattrochi,d pookotD Pookot,m iwahashiM Iwahashi,r dahiyaR Dahiya,

    For similar abstracts research abstracts see: abstracts research

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    A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Molecular pharmacology

    VOLUME: 72

    Page Numbers: 1457-65

    Journal Abbreviation: Mol. Pharmacol.

    ISSN: 1521-0111

    DAY: 4

    MONTH: 09

    YEAR: 2007

    A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Information

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    LANGUAGE: eng

    NlmUniqueID: 35623

    A dioxin-responsive enhancer 3' of the human CYP1A2 gene. Keywords Mesh Terms:

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    Grant and Affiliation Information for A dioxin-responsive enhancer 3' of the human CYP1A2 gene.

    AFFILIATION: Department of Urology, San Francisco Veterans Affairs Medical Center and UCSF, 4150 Clement Street, San Francisco, CA 94121, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDDK

    GRANT: T32DK07790

    ACRONYM: DK

    MEDLINETA: Mol Pharmacol

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