AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes

Karchner, Sibel I.; Franks, Diana G.; Hahn, Mark E.

doi:10.1042/bj20050713

Cited by 151Toxic Organic Pollutants ImpactEnvironmental Toxicology and EcotoxicologyPharmacogenetics and Drug Metabolism

AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes

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Karchner, Sibel I., Franks, Diana G., Hahn, Mark E.·2005·Biochemical Journal

DOI 10.1042/bj20050713PMC PMC1317674

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Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates gene expression following activation by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) or a variety of other synthetic and natural compounds. Previous studies have identified two AHR genes, AHR1 and AHR2, in zebrafish (Danio rerio), a widely used model species for studying vertebrate development and an emerging model in developmental toxicology. Zebrafish AHR2 binds TCDD with high affinity, is transcriptionally active and has a major role in mediating the developmental toxicity of TCDD. Zebrafish AHR1 lacks the ability to bind TCDD and activate transcription, and has no known function. In the present study, we report a new zebrafish AHR, designated AHR1B, which shares 34% amino acid sequence identity with AHR1 (AHR1A). The ahr1b gene resides on chromosome 22, adjacent to ahr2, whereas the ahr1a gene is located on chromosome 16. AHR1B is expressed in embryos as early as 24 hours post-fertilization and increases through the next 2 days, but expression is not inducible by TCDD. In contrast with the previously identified AHR1A, in vitro-expressed AHR1B protein exhibits specific, high-affinity binding of [3H]TCDD. Furthermore, AHR1B is able to activate the transcription of a reporter gene under the control of AHR response elements with an efficacy comparable with that of AHR2, but with a higher EC50. We speculate that AHR1B may have a physiological role, such as in embryonic development, whereas AHR2 mediates the response to xenobiotics.

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zfAHR1b has lower TCDD affinity than zfAHR2 and is classified as medium affinity based on an approximately 8-fold lower potency for TCDD-dependent transcription activation in COS-7 cells.
“However, based on the approximately 8-fold lower potency of TCDD-dependent activation of transcription in COS-7 cells transiently transfected with zfAHR1b, compared to those containing zfAHR2, zfAHR1b is designated as having a ‘medium’ TCDD-binding affinity (29).”
From Comparative Analysis of Homology Models of the Ah Receptor Ligand Binding Domain: Verification of Structure–Function Predictions by Site-Directed Mutagenesis of a Nonfunctional Receptor (2013) · cites this paper as [29]
The Functional characterization section reports that TCDD-dependent transcriptional activation in COS-7 cells had apparent EC50 values of 5.9 nM for AHR1B and 0.7 nM for AHR2—approximately an eightfold difference. The Functional implications section also says AHR1B has somewhat lower TCDD-binding affinity than AHR2. However, the paper does not designate AHR1B’s affinity as “medium”; it describes its TCDD binding as high-affinity. (LLM, conf=0.88)
Experimental — accuracy not yet measured
zfAHR1a does not detectably bind TCDD, bind DNA, or activate transcription in response to TCDD.
“one of which (AHR1a) has been shown previously to lack the ability to bind TCDD and DNA and to activate transcription in the presence of TCDD [28,29].”
From Comparative Analysis of Homology Models of the Ah Receptor Ligand Binding Domain: Verification of Structure–Function Predictions by Site-Directed Mutagenesis of a Nonfunctional Receptor (2013) · cites this paper as [29]
The Functional characterization section reports that AHR1A failed to bind TCDD and did not activate a reporter above the no-AHR control, including after TCDD exposure. Our copy does not establish the separate claim that AHR1A cannot bind DNA. (LLM, conf=0.85)
Experimental — accuracy not yet measured
zfAHR2 and zfAHR1b bind TCDD with high and medium affinity, respectively, whereas zfAHR1a does not bind TCDD.
“while zfAHR2 and zfAHR1b can bind TCDD with high and medium affinity, respectively, zfAHR1a fails to bind TCDD (28,29).”
From Comparative Analysis of Homology Models of the Ah Receptor Ligand Binding Domain: Verification of Structure–Function Predictions by Site-Directed Mutagenesis of a Nonfunctional Receptor (2013) · cites this paper as [29]
The Functional characterization section reports high-affinity TCDD binding by AHR2 and no binding by AHR1A. It finds that AHR1B binds TCDD with somewhat lower affinity than AHR2, but explicitly describes AHR1B’s binding as high-affinity, not medium-affinity. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Zebrafish have three AHRs: zfAHR1a, zfAHR1b, and zfAHR2.
“Zebrafish (Danio rerio) possess three AHRs, one of which (AHR1a) has been shown previously to lack the ability to bind TCDD and DNA and to activate transcription in the presence of TCDD [28,29].”
From Comparative Analysis of Homology Models of the Ah Receptor Ligand Binding Domain: Verification of Structure–Function Predictions by Site-Directed Mutagenesis of a Nonfunctional Receptor (2013) · cites this paper as [29]
zfAHR2 binds TCDD with high affinity, with a Kd of about 1 nM.
“While zfAHR2 has a high affinity for TCDD (Kd ~1 nM), that for zfAHR1b is lower, although it could not be quantitatively determined due to experimental limitations (29).”
From Comparative Analysis of Homology Models of the Ah Receptor Ligand Binding Domain: Verification of Structure–Function Predictions by Site-Directed Mutagenesis of a Nonfunctional Receptor (2013) · cites this paper as [29]

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AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish
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Influence of TCDD on Zebrafish CYP1B1 Transcription during Development
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Exposure to the AhR agonist cyprodinil impacts the cardiac development and function of zebrafish larvae
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Malformation of certain brain blood vessels caused by TCDD activation of Ahr2/Arnt1 signaling in developing zebrafish
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The emerging contaminant 3,3′-dichlorobiphenyl (PCB-11) impedes Ahr activation and Cyp1a activity to modify embryotoxicity of Ahr ligands in the zebrafish embryo model (Danio rerio)
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Reproductive Impairment of Great Lakes Lake Trout by Dioxin-Like Chemicals
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Amino Acid Substitutions in the Aryl Hydrocarbon Receptor Ligand Binding Domain Reveal YH439 As an Atypical AhR Activator
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Molecular and Functional Characterization of a Novel Aryl Hydrocarbon Receptor Isoform, AHR1β, in the Chicken (Gallus gallus)
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An Aryl Hydrocarbon Receptor from the SalamanderAmbystoma mexicanumExhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
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Authors: Karchner, S. I., Franks, D. G., & Hahn, M. E.
Affiliations: Woods Hole Oceanographic Institution (US)
ORCID: Karchner, Sibel I.
Hahn, Mark E.
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 2005-11-08
Volume: 392
Issue: 1
Pages: 153-161
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj20050713
PMC: PMC1317674
OpenAlex: W1980302096
Cited by: 151
References: 53
Citations by year: 2026: 4 · 2025: 4 · 2024: 6 · 2023: 3 · 2021: 4 · 2020: 7 · 2019: 8 · 2018: 13 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 11 · 2013: 7 · 2012: 4
FWCI: 5.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Woods Hole Oceanographic Institution
National Institutes of Health
National Institute of Environmental Health Sciences (R01ES006272)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: aryl hydrocarbon receptor, AHR2, zebrafish, transcriptional activation, gene expression, embryonic development, developmental toxicity, xenobiotic response, gene duplication, chromosome 22
MeSH terms: Amino Acid Sequence, Animals, Chlorocebus aethiops, Molecular Sequence Data, Phylogeny, Protein Binding, Transcription, Genetic, Zebrafish, Sequence Alignment, Conserved Sequence, Sequence Homology, Amino Acid, Receptors, Aryl Hydrocarbon, Gene Expression Regulation, Developmental, COS Cells, Gene Order, Zebrafish Proteins

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AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes

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