A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia.

A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Research Abstract Details 

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A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Abstract Text:

Steven P Rivera,Feng Wang,Sirkku T Saarikoski,Robert T Taylor,Brett Chapman,Ruixue Zhang,Oliver Hankinson,

Cytochrome P4502S1 (CYP2S1) is expressed at high levels in epithelial tissues and is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) via the aryl hydrocarbon receptor (AHR). Transcriptional initiation of mouse Cyp2s1 was found to occur at three regions, approximately 198, 102, and 22 nucleotides from the translational initiation codon. Approximately 400 nucleotides upstream of its translational initiation codon, mouse Cyp2s1 contains three overlapping xenobiotic-responsive element (XRE) sequences, which make a major contribution toward dioxin inducibility. Each XRE sequence in this trimeric XRE can bind the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer in a dioxin-dependent fashion in vitro and can mediate dioxin-dependent transcription. Cyp2s1 is also markedly inducible by hypoxia. Induction is dependent on hypoxiainducible factor-1 (HIF-1) and is mediated in large part by three overlapping hypoxia response elements (HREs) embedded within the trimeric XRE segment. Although each HRE within this segment can bind HIF-1alpha/ARNT in vitro, the most 3' HRE contributes the most toward hypoxia inducibility. AHR/ARNT and HIF-1alpha/ARNT dimers bind to the region containing the trimeric XRE segment of the endogenous Cyp2s1 gene in vivo in a dioxin-dependent fashion and hypoxia-dependent fashion, respectively. These observations identify a novel regulatory cassette that mediates changes in Cyp2s1 expression.

A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Publishing Authors By Initials

SP Rivera,F Wang,ST Saarikoski,RT Taylor,B Chapman,R Zhang,O Hankinson,

For similar pharmaceutical preparations: xenobiotics research abstracts see: pharmaceutical preparations: xenobiotics research

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A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 10881-93

Journal Abbreviation:

ISSN: 0021-9258

DAY: 2

MONTH: 02

YEAR: 2007

A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Keywords Mesh Terms:

KEYWORDS: Xenobiotics

MESH TERMS: pharmacology

Chemical & Substance for Abstract: A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Information

Substance Name: CYP2S1 protein, human

Registry Number: EC 1.14.-

Grant and Affiliation Information for A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia.

AFFILIATION: Department of Pathology and Laboratory Medicine and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: R01 ES015384

ACRONYM: ES

MEDLINETA: J Biol Chem

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