Cited by 31interferon and immune responsesCytokine Signaling Pathways and InteractionsGenomics and Chromatin Dynamics

The IRF-2 DNA binding domain facilitates the activation of the class II transactivator (CIITA) type IV promoter by IRF-1

Xi, Hongkang, Blanck, George·2003·Molecular Immunology

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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Crossref · 10.1016/s0161-5890(02)00214-6

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Authors
Xi, H., & Blanck, G.
Affiliations
University of South Florida (US)
Corresponding author
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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