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

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

doi:10.1042/bj20050713

Cited by 127 publications

(167 citation statements)

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“…We used COS-7 cells because they express very low levels of endogenous AHR and have been widely used to characterize AHR proteins from a variety of species (Abnet et al 1999b;Karchner et al 2002;Karchner et al 2005). The salmon AHR2s were transiently expressed in COS-7 cells along with the rainbow trout ARNT2b, and a luciferase reporter gene under the control of AHREs.…”

Section: Ahr2 Transcriptional Activity In Cos-7 Cellsmentioning

confidence: 99%

Functional properties of the four Atlantic salmon (Salmo salar) aryl hydrocarbon receptor type 2 (AHR2) isoforms

Hansson

Hahn

2008

Aquatic Toxicology

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor through which organochlorine contaminants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and some polycyclic aromatic hydrocarbons induce toxicity and altered gene expression. Atlantic salmon has multiple AHR genes, of which two belong to the AHR1 clade and four belong to the AHR2 clade. The four AHR2 forms (α, β, γ, δ) are more highly expressed than the AHR1 (α, β,) forms and all six AHRs are highly similar in pairs, likely originating from a whole-genome duplication in the salmonid ancestor. It has been speculated that having multiple AHRs contributes to the very high sensitivity of salmonid species to TCDD and related chemicals. To test the hypothesis that all four salmon AHR2 proteins are expressed and functional, we measured mRNA transcription for each AHR2 inside several tissues, cloned the cDNAs and evaluated the functional properties of the expressed proteins. Analysis by real-time PCR revealed that the receptors showed differences in transcript levels among salmon tissues and that in general AHR2α was transcribed at higher levels than the other three AHR2s. Velocity sedimentation analysis showed that all four in vitro-expressed AHR2 proteins exhibit specific, high-affinity binding of [ 3 H]TCDD. When expressed in COS-7 cells, all four AHR2 proteins were able to drive the expression of a reporter gene under control of murine CYP1A1 enhancer elements. From EC 50 values determined in TCDD concentration-response experiments, all four salmon AHR2s show similar sensitivity to TCDD. In summary, all four Atlantic salmon AHR2 appear to function in AHR-mediated signaling, suggesting that all four proteins are involved in TCDD-mediated toxicity.

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Section: Ahr2 Transcriptional Activity In Cos-7 Cellsmentioning

confidence: 99%

Functional properties of the four Atlantic salmon (Salmo salar) aryl hydrocarbon receptor type 2 (AHR2) isoforms

Hansson

Hahn

2008

Aquatic Toxicology

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“…AHR1 sequence signatures predict toxicity of dioxin-like compounds in birds (Farmahin et al, 2013). In contrast, AHR2 mediates TCDD toxicity in developing zebrafish (Prasch et al, 2003), even though TCDD is an in vitro AHR1B agonist (Karchner et al, 2005).…”

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confidence: 99%

Subfunctionalization of Paralogous Aryl Hydrocarbon Receptors from the FrogXenopus Laevis: Distinct Target Genes and Differential Responses to Specific Agonists in a Single Cell Type

2016

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Gene duplication confers genetic redundancy that can facilitate subfunctionalization, the partitioning of ancestral functions between paralogs. We capitalize on a recent genome duplication in Xenopus laevis (African clawed frog) to interrogate possible functional differentiation between alloalleles of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates toxicity of dioxin-like compounds and plays a role in the physiology and development of the cardiovascular, hepatic, and immune systems in vertebrates. X. laevis has 2 AHR genes, AHR1a and AHR1b. To test the hypothesis that the encoded proteins exhibit different molecular functions, we used TALENs in XLK-WG cells, generating mutant lines lacking functional versions of each AHR and measuring the transcriptional responsiveness of several target genes to the toxic xenobiotic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the candidate endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ). Mutation of either AHR1a or AHR1b reduced TCDD induction of the canonical AHR target, Cytochrome P4501A6, by 75%, despite the much lower abundance of AHR1b in wild-type cells. More modestly induced target genes, encoding aryl hydrocarbon receptor repressor (AHRR), spectrin repeat-containing nuclear envelope protein 1 (SYNE-1), and gap junction protein gamma 1 (GJC1), were regulated solely by AHR1a. AHR1b was responsible for CYP1A6 induction by FICZ, while AHR1a mediated FICZ induction of AHRR. We conclude that AHR1a and AHR1b have distinct transcriptional functions in response to specific agonists, even within a single cell type. Functional analysis of frog AHR paralogs advances the understanding of AHR evolution and as well as the use of frog models of developmental toxicology such as FETAX.

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“…To use zebrafish as a model to study TCDD developmental toxicity, it was essential to identify and characterize the zebrafish AHR signaling pathway, and much is now known about its components. Three forms of the AHR (zfAHR1, zfAHR1B, and zfAHR2) have been identified in zebrafish (Tanguay et al, 1999;Andreasen et al, 2002a;Karchner et al, 2005), and morpholino knockdown of zfAHR2 has identified it as the receptor that binds TCDD, leading to downstream effects (Prasch et al, 2003;Teraoka et al, 2003;Dong et al, 2004). In untreated zebrafish liver cells, zfAHR2 has been shown to shuttle between the cytoplasm and nucleus.…”

mentioning

confidence: 99%

Identification of Zebrafish ARNT1 Homologs: 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicity in the Developing Zebrafish Requires ARNT1

Prasch¹,

Tanguay²,

Mehta³

et al. 2005

Mol Pharmacol

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To use the zebrafish (Danio rerio) as a model to study 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) developmental toxicity, it is essential to know which proteins are involved in mediating toxicity. Previous work has identified zfAHR2 as the receptor that binds TCDD mediating downstream responses. Although zfARNT2b can form a functional heterodimer with zfAHR2 in vitro, zfarnt2 null mutants show no protection against endpoints of TCDD developmental toxicity, demonstrating that zfARNT2b cannot be the physiological dimerization partner for zfAHR2 mediating responses to TCDD in zebrafish embryos. The purpose of the current study was to identify an alternate dimerization partner(s) for zfAHR2 that may function to mediate TCDD developmental toxicity. By searching zebrafish genomic sequence and using the polymerase chain reaction-based rapid amplification of cDNA ends technique, three forms of cDNA that seem to be alternate mRNA splice variants of a zebrafish homolog of ARNT1 were detected. Analysis of the zfARNT1 proteins in vitro demonstrates that the two longest forms of zfARNT1, zfARNT1b and zfARNT1c, can form functional heterodimers with zfAHR2. However, the shortest form, zfARNT1a, seems to be nonfunctional with zfAHR2 in vitro. To determine whether a zfARNT1 protein functions with zfAHR2 in vivo, a morpholino targeted against the 5Ј end of zfARNT1 (zfarnt1-MO) was used. Injection of the zfarnt1-MO before TCDD treatment significantly decreases the induction of zfCYP1A mRNA and protein. In addition, zfarnt1 morphants show complete protection against TCDD-induced pericardial edema and show partial protection against reduced blood flow and craniofacial malformations caused by TCDD, demonstrating the role of zfARNT1 proteins in mediating these responses.

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

Cited by 127 publications

References 53 publications

Functional properties of the four Atlantic salmon (Salmo salar) aryl hydrocarbon receptor type 2 (AHR2) isoforms

Functional properties of the four Atlantic salmon (Salmo salar) aryl hydrocarbon receptor type 2 (AHR2) isoforms

Subfunctionalization of Paralogous Aryl Hydrocarbon Receptors from the FrogXenopus Laevis: Distinct Target Genes and Differential Responses to Specific Agonists in a Single Cell Type

Identification of Zebrafish ARNT1 Homologs: 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicity in the Developing Zebrafish Requires ARNT1

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