PUBLICATION
Zebrafish IRF1, IRF3, and IRF7 Differentially Regulate IFNΦ1 and IFNΦ3 Expression through Assembly of Homo- or Heteroprotein Complexes
- Authors
- Feng, H., Zhang, Q.M., Zhang, Y.B., Li, Z., Zhang, J., Xiong, Y.W., Wu, M., Gui, J.F.
- ID
- ZDB-PUB-160809-13
- Date
- 2016
- Source
- Journal of immunology (Baltimore, Md. : 1950) 197(5): 1893-904 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Binding Sites
- Gene Expression Regulation*
- Interferon Regulatory Factor-1/genetics*
- Interferon Regulatory Factor-1/immunology
- Interferon Regulatory Factor-3/genetics*
- Interferon Regulatory Factor-3/immunology
- Interferon Regulatory Factor-7/genetics*
- Interferon Regulatory Factor-7/immunology
- Interferons/genetics*
- Interferons/immunology
- Promoter Regions, Genetic
- Protein Binding
- Rhabdoviridae
- Rhabdoviridae Infections/immunology*
- Rhabdoviridae Infections/metabolism
- Signal Transduction
- Transcription, Genetic
- Transcriptional Activation
- Zebrafish/genetics
- Zebrafish/immunology
- PubMed
- 27496972 Full text @ J. Immunol.
Citation
Feng, H., Zhang, Q.M., Zhang, Y.B., Li, Z., Zhang, J., Xiong, Y.W., Wu, M., Gui, J.F. (2016) Zebrafish IRF1, IRF3, and IRF7 Differentially Regulate IFNΦ1 and IFNΦ3 Expression through Assembly of Homo- or Heteroprotein Complexes. Journal of immunology (Baltimore, Md. : 1950). 197(5):1893-904.
Abstract
In mammals, IFN regulatory factor (IRF)1, IRF3, and IRF7 are three critical transcription factors that are pivotal for cooperative regulation of the type I IFN response. In this study, we explored the relative contribution of zebrafish (Danio rerio) IRF1 (DrIRF1), IRF3 (DrIRF3), and IRF7 (DrIRF7) (DrIRF1/3/7) to zebrafish IFNΦ1 (DrIFNΦ1) and IFNΦ3 (DrIFNΦ3) (DrIFNΦ1/3) activation. Following spring viremia of carp virus infection, DrIFNΦ1/3 and DrIRF1/3/7 transcripts are significantly induced in zebrafish tissues, which correlates with the replication of spring viremia of carp virus. DrIRF1/3/7 selectively bind to the IRF-binding element/IFN-stimulated regulatory element sites of DrIFNΦ1/3 promoters, with the exception that DrIRF3 has no preference for two IRF-binding element/IFN-stimulated regulatory element motifs within the DrIFNΦ3 promoter. Consistently, DrIRF3 alone activates DrIFNΦ1, but not DrIFNΦ3; DrIRF7 predominantly stimulates DrIFNΦ3; and DrIRF1 has similar potential to DrIFNΦ1 and DrIFNΦ3. Strikingly, DrIRF3 facilitates the binding of DrIRF1 and DrIRF7 to both zebrafish IFN promoters, and so does DrIRF7 for the binding of DrIRF1, particularly to the DrIFNΦ3 promoter. These binding properties correlate with differential responses of DrIFNΦ1 and DrIFNΦ3 to the combinatory stimulation of DrIRF1/3/7, depending on their relative amounts. Similar to the dual roles of human IRF3 in regulating IRF7-activated IFNα genes, DrIRF3 exerts dual effects on DrIRF1-mediated DrIFNΦ3 gene expression: an inhibitory effect at lower concentrations and a synergistic effect at higher concentrations. These data provide evidence that fish and mammals have evolved a similar IRF-dependent regulatory mechanism fine-tuning IFN gene activation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping