The IRF-2 DNA binding domain facilitates the activation of the class II transactivator (CIITA) type IV promoter by IRF-1
Abstract
IFN-gamma induced transcription of class II transactivator (CIITA), a major regulator of MHC class II gene expression, is directed by the CIITA type IV promoter. The IFN-gamma activation of the CIITA type IV promoter is mediated by STAT1 and IRF-1, which bind to the GAS and IRF-E of the promoter, respectively. We and others have determined that IRF-2, another member of the IRF family, also activates the CIITA type IV promoter, by binding to the IRF-E. Also, IRF-2 cooperates with IRF-1 to activate the promoter. DNA binding analyses determined that IRF-1 and IRF-2 can co-occupy the IRF-E of the CIITA type IV promoter. To further understand the mechanism of IRF-1 and IRF-2 cooperativity in the activation of CIITA type IV promoter, we characterized the binding of IRF-1 and IRF-2 to the CIITA IRF-E and mapped the domains of IRF-2 required for the cooperative transactivation. Off-rate experiments revealed that the IRF-2/IRF-E complex was more stable than the IRF-1/IRF-E complex and that the affinity of IRF-1 for the IRF-E was increased when IRF-1 co-occupied the IRF-E with IRF-2. Deletion analysis of functional domains of IRF-2 revealed that a previously described latent activation domain of IRF-2 was essential for IRF-2 transactivation and participated in cooperative activation of the CIITA promoter by IRF-1 and IRF-2. However, the DNA binding domain of IRF-2 was sufficient for cooperativity with IRF-1 in the activation of the CIITA type IV promoter. DNA binding assay demonstrated that, like the full-length IRF-2, the IRF-2 DNA binding domain could co-occupy the CIITA IRF-E with IRF-1.
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Previous studies found IRF2 activates transcription of some genes involved in the innate immune response.
“Previous studies found IRF2 activates transcription of some genes involved in the innate immune response (23, 44 -46).”
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肺鱼干扰素调节因子 1 基因(irf-1)的克隆及其在肉鳍类中的分子进化
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factor-2 alters its N-terminal DNA-binding activity
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CLONING AND CHARACTER ANALYSES OF IRF-1 GENE OF CHILOSCYLLIUM PLAGIOSUM
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- Authors
- Xi, H., & Blanck, G.
- Affiliations
- University of South Florida (US)
- Corresponding author
- Blanck, George
- ORCID
- Blanck, George
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 39
- Issue
- 11
- Pages
- 677-684
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W2002111319
- Cited by
- 31
- References
- 43
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2017: 3 · 2016: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Moffitt Cancer Center
- National Institutes of Health (5r01ca081497-04)
- University of Texas MD Anderson Cancer Center
- National Cancer Institute (R01 CA81497-01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- IRF2, IRF1, interferon-gamma, MHC class II gene expression, STAT1, DNA-binding domain, transcriptional activation
- MeSH terms
- Animals, Binding Sites, DNA, DNA-Binding Proteins, Gene Expression Regulation, Interferon-gamma, Nuclear Proteins, Phosphoproteins, Promoter Regions, Genetic, Repressor Proteins, Transcription Factors, Trans-Activators, Mice, Knockout, Interferon Regulatory Factor-2, Interferon Regulatory Factor-1, Mice
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