PUBLICATION
Duplicate aryl hydrocarbon receptor repressor genes (ahrr1 and ahrr2) in the zebrafish Danio rerio: Structure, function, evolution, and AHR-dependent regulation in vivo
- Authors
- Evans, B.R., Karchner, S.I., Franks, D.G., and Hahn, M.E.
- ID
- ZDB-PUB-050831-4
- Date
- 2005
- Source
- Archives of biochemistry and biophysics 441(2): 151-167 (Journal)
- Registered Authors
- Hahn, Mark E.
- Keywords
- Aryl hydrocarbon receptor, Aryl hydrocarbon receptor repressor, TCDD, Zebrafish, Repression, Evolution, Gene duplication, Synteny, CYP1A, ZF-L cell line
- MeSH Terms
-
- Receptors, Aryl Hydrocarbon/genetics
- Receptors, Aryl Hydrocarbon/metabolism*
- Structure-Activity Relationship
- Zebrafish/genetics*
- Zebrafish/metabolism*
- Base Sequence
- Animals
- Repressor Proteins/analysis
- Repressor Proteins/chemistry*
- Repressor Proteins/genetics
- Repressor Proteins/metabolism*
- Evolution, Molecular*
- Genes, Duplicate/genetics*
- Sequence Homology, Amino Acid
- Zebrafish Proteins/analysis
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Molecular Sequence Data
- Amino Acid Sequence
- PubMed
- 16122694 Full text @ Arch. Biochem. Biophys.
Citation
Evans, B.R., Karchner, S.I., Franks, D.G., and Hahn, M.E. (2005) Duplicate aryl hydrocarbon receptor repressor genes (ahrr1 and ahrr2) in the zebrafish Danio rerio: Structure, function, evolution, and AHR-dependent regulation in vivo. Archives of biochemistry and biophysics. 441(2):151-167.
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The recently identified AHR repressor (AHRR) forms a negative feedback loop with the AHR. We investigated AHRR structure, function, evolution, and regulation in zebrafish, a powerful model in developmental biology and toxicology. We identified and cloned two distinct AHRR cDNAs that encode predicted proteins of 550 (AHRR1) and 573 (AHRR2) amino acids. The ahrr1 and ahrr2 genes map to zebrafish chromosomes 24 and 2, respectively, both of which share conserved synteny with human chromosome 5, the location of human AHRR. Mapping and phylogenetic analysis show that AHRR1 and AHRR2 are co-orthologs of the mammalian AHRR. In transient transfection assays, AHRR1 and AHRR2 repressed constitutive and TCDD-inducible transactivation by AHR2. Expression of both AHRR mRNAs was induced in ZF-L cells by AHR agonists but not by non-agonists. TCDD induced AHRR1 and AHRR2 expression in a dose-dependent manner in ZF-L cells, with EC(50) values similar to those for induction of CYP1A. Both AHRRs were expressed and induced by TCDD in zebrafish embryos. Thus, zebrafish possess duplicate AHR-regulated AHRR paralogs that act in a negative feedback loop to repress the AHR signaling pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping