Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer
Autor: | Paula A. Bank, Eveline F. Yao, Cynthia L. Phelps, Michael S. Denison, Patricia A. Harper |
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Rok vydání: | 1992 |
Předmět: |
Male
Polychlorinated Dibenzodioxins Swine Trout Receptors Drug Guinea Pigs Molecular Sequence Data Mutant Hamster Biology urologic and male genital diseases Toxicology Binding Competitive Rats Sprague-Dawley Mice chemistry.chemical_compound Cytosol Species Specificity Cricetinae medicine Animals Humans Enhancer Cells Cultured Pharmacology Genetics Base Sequence Mesocricetus Oligonucleotide Pollution Molecular biology In vitro Rats Receptors Aryl Hydrocarbon chemistry Mechanism of action Mice Inbred CBA Cattle Rabbits medicine.symptom DNA Transcription Factors |
Zdroj: | European Journal of Pharmacology: Environmental Toxicology and Pharmacology. 228:85-94 |
ISSN: | 0926-6917 |
DOI: | 10.1016/0926-6917(92)90016-6 |
Popis: | The Ah receptor (AhR) mediates many, if not all, of the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons. Although wide variations in species sensitivity to these compounds have been observed, numerous biochemical and physiochemical characteristics of the AhR appear similar among species. We have examined the ability of cytosolic AhR, from a variety of species (rat, rabbit, guinea pig, hamster, mouse, cow, sheep, fish, chicken and human), to transform and bind to its cognate DNA recognition sequence, the dioxin responsive enhancer (DRE), to evaluate the importance of these events in species variations in TCDD responsiveness. Gel retardation analysis using a murine DRE oligonucleotide has revealed that cytosolic AhR from a wide variety of species can transform in vitro and bind to the DRE and demonstrates that all of the factors necessary for AhR transformation and DNA binding are present in cytosol. In addition, DNA-binding analysis using a series of mutant DRE oliognucleotides has indicated no apparent species- or ligand-dependent, nucleotide-specific difference in AhR binding to the DRE. These studies support a highly conserved nature of the DRE and AhR (at least in DNA binding) and imply that a sequence closely related to the murine consensus DRE sequence is responsible for conferring AhR-dependent, TCDD responsiveness in each of these species. |
Databáze: | OpenAIRE |
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