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AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes
Open accessAbstract
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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“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]
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“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]
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“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]
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“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].”
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“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).”
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“Three zebrafish AHRs have been described (zAHR1a, zfAHR1b and zfAHR2)”
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“As expected, TCDD can stimulate gene expression by zfAHR2 and zfAHR1b, but not by zfAHR1a (28,29).”
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Cites
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Research works printed but not linked: 2
- Prasch, 2005, Identification of zebrafish ARNT1 homologs: TCDD developmental toxicity in zebrafish requires ARNT1, Toxicol. Sci., 84, 18
- Karchner, 2004, Pufferfish (Fugu rubripes) aryl hydrocarbon receptors: unusually high diversity in a compact genome, Mar. Environ. Res., 58, 139
Cited by
Sorted by citations
Groh, K. J., Pakdel, F., Segner, H. E., Kah, O., & Eggen, R. I. L. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.03.005 · Cited by 345
Incardona, J. P., Day, H. L., Collier, T. K., & Scholz, N. L. (2006) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2006.09.018 · Cited by 319
Billiard, S. M., Timme‐Laragy, A. R., Wassenberg, D. M., Cockman, C. J., & Giulio, R. T. D. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfl011 · Cited by 312
Incardona, J. P., Linbo, T. L., & Scholz, N. L. (2011) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2011.09.010 · Cited by 181
Billiard, S. M., Meyer, J. N., Wassenberg, D. M., Hodson, P. V., & Giulio, R. T. D. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm303 · Cited by 182
Metadata
- Authors
- Karchner, S. I., Franks, D. G., & Hahn, M. E.
- Affiliations
- Woods Hole Oceanographic Institution (US)
- 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
- 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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