PUBLICATION
Identification and functional characterization of two highly divergent aryl hydrocarbon receptors (AHR1 and AHR2) in the teleost Fundulus heteroclitus. Evidence for a novel subfamily of ligand-binding basic helix loop helix-Per-ARNT-Sim (bHLH-P
- Authors
- Karchner, S.I., Powell, W.H., and Hahn, M.E.
- ID
- ZDB-PUB-020701-1
- Date
- 1999
- Source
- The Journal of biological chemistry 274(47): 33814-33824 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Base Sequence
- Basic Helix-Loop-Helix Transcription Factors
- DNA, Complementary
- DNA-Binding Proteins/chemistry
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Fishes
- Ligands
- Molecular Sequence Data
- Phylogeny
- Protein Binding
- Protein Isoforms/chemistry*
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Receptors, Aryl Hydrocarbon/chemistry*
- Receptors, Aryl Hydrocarbon/genetics
- Receptors, Aryl Hydrocarbon/metabolism
- Sequence Homology, Amino Acid
- Trans-Activators/metabolism*
- PubMed
- 10559277 Full text @ J. Biol. Chem.
Citation
Karchner, S.I., Powell, W.H., and Hahn, M.E. (1999) Identification and functional characterization of two highly divergent aryl hydrocarbon receptors (AHR1 and AHR2) in the teleost Fundulus heteroclitus. Evidence for a novel subfamily of ligand-binding basic helix loop helix-Per-ARNT-Sim (bHLH-P. The Journal of biological chemistry. 274(47):33814-33824.
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor through which 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds cause altered gene expression and toxicity. The AHR belongs to an emerging multigene family of transcription factors possessing basic helix loop helix (bHLH) and Per-ARNT-Sim (PAS) domains. Most bHLH-PAS proteins occur as duplicates or "paralog groups" in mammals, but only a single mammalian AHR has been identified. Here we report the cDNA cloning of two distinct AHRs, designated FhAHR1 and FhAHR2, from a single vertebrate species, the teleost Fundulus heteroclitus (Atlantic killifish). Both Fundulus AHR proteins possess bHLH and PAS domains that are closely related to those of the mammalian AHR. FhAHR1 and FhAHR2 are highly divergent (40% overall amino acid identity; 61% identity in the N-terminal half), suggesting that they arose from a gene duplication predating the divergence of mammals and fish. Photoaffinity labeling with 2-azido-3-[(125)I]iodo-7, 8-dibromodibenzo-p-dioxin and velocity sedimentation analysis using 2,3,7,8-[1,6-(3)H]TCDD showed that both FhAHR1 and FhAHR2 exhibit specific, high-affinity binding of dioxins. Both AHRs also showed specific, TCDD- and ARNT-dependent interactions with a mammalian xenobiotic response element. The two Fundulus AHR genes displayed different tissue-specific patterns of expression; FhAHR1 transcripts were primarily expressed in brain, heart, ovary, and testis, while FhAHR2 transcripts were equally abundant in many tissues. Phylogenetic analysis demonstrated that Fundulus AHR1 is an ortholog of mammalian AHRs, while AHR2 forms in Fundulus and other fish are paralogous to Fundulus AHR1 and the mammalian AHRs and thus represent a novel vertebrate subfamily of ligand-binding AHRs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping