Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer

Paula A. Bank, Eveline F. Yao, Cynthia L. Phelps, Patricia A. Harper, Michael S. Denison

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalEuropean Journal of Pharmacology: Environmental Toxicology and
Volume228
Issue number2-3
DOIs
StatePublished - Sep 1 1992
Externally publishedYes

Fingerprint

Dioxins
DNA
Oligonucleotides
Aromatic hydrocarbons
Nucleotides
Fish
Rats
Gels
Ligands
Halogenated Hydrocarbons
Aromatic Hydrocarbons
Aryl Hydrocarbon Receptors
Poisons
Cricetinae
Cytosol
Chickens
Sheep
Guinea Pigs
Fishes
Rabbits

Keywords

  • Ah receptor
  • TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

ASJC Scopus subject areas

  • Pollution
  • Pharmacology
  • Toxicology

Cite this

Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer. / Bank, Paula A.; Yao, Eveline F.; Phelps, Cynthia L.; Harper, Patricia A.; Denison, Michael S.

In: European Journal of Pharmacology: Environmental Toxicology and, Vol. 228, No. 2-3, 01.09.1992, p. 85-94.

Research output: Contribution to journalArticle

Bank, Paula A. ; Yao, Eveline F. ; Phelps, Cynthia L. ; Harper, Patricia A. ; Denison, Michael S. / Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer. In: European Journal of Pharmacology: Environmental Toxicology and. 1992 ; Vol. 228, No. 2-3. pp. 85-94.
@article{18361b56cd9c4e07ad10ebe43a224df9,
title = "Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer",
abstract = "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.",
keywords = "Ah receptor, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)",
author = "Bank, {Paula A.} and Yao, {Eveline F.} and Phelps, {Cynthia L.} and Harper, {Patricia A.} and Denison, {Michael S.}",
year = "1992",
month = "9",
day = "1",
doi = "10.1016/0926-6917(92)90016-6",
language = "English (US)",
volume = "228",
pages = "85--94",
journal = "Environmental Toxicology and Pharmacology",
issn = "1382-6689",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer

AU - Bank, Paula A.

AU - Yao, Eveline F.

AU - Phelps, Cynthia L.

AU - Harper, Patricia A.

AU - Denison, Michael S.

PY - 1992/9/1

Y1 - 1992/9/1

N2 - 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.

AB - 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.

KW - Ah receptor

KW - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

UR - http://www.scopus.com/inward/record.url?scp=0026731745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026731745&partnerID=8YFLogxK

U2 - 10.1016/0926-6917(92)90016-6

DO - 10.1016/0926-6917(92)90016-6

M3 - Article

VL - 228

SP - 85

EP - 94

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

SN - 1382-6689

IS - 2-3

ER -