Cited by 64interferon and immune responsesGenomics and Chromatin DynamicsCytokine Signaling Pathways and Interactions

Interferon Regulatory Factors and TFIIB Cooperatively Regulate Interferon-Responsive Promoter Activity In Vivo and In Vitro

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Wang, I-Ming, Blanco, Jorge C. G., Tsai, Sophia Y., Tsai, Ming-Jer, Ozato, Keiko·1996·Molecular and Cellular Biology

Abstract

Interferon regulatory factors (IRFs) bind to the interferon-stimulated response element (ISRE) and regulate interferon- and virus-mediated gene expression. IRF-1 acts as a transcriptional activator, while IRF-2 acts as a repressor. Here we show that IRF-1 and IRF-2 bind to both cellular TFIIB, a component of the basal transcription machinery, and recombinant TFIIB (rTFIIB) and that this protein-protein interaction facilitates binding of IRFs to the ISRE. A functional interaction between TFIIB and IRF was assessed by a newly established in vitro transcription assay in which recombinant IRF-1 (rIRF-1) stimulated transcription specifically from an ISRE-containing template. With this assay we show that rIRF-1 and rTFIIB cooperatively enhance the ISRE promoter in vitro. We found that the activity of an ISRE-containing promoter was cooperatively enhanced upon cotransfection of TFIIB and IRF-1 cDNAs into P19 embryonal carcinoma cells, further demonstrating functional interactions in vivo. The cooperative enhancement by TFIIB and IRF-1 was independent of the TATA sequence in the ISRE promoter but dependent on the initiator sequence (Inr) and was abolished when P19 cells were induced to differentiate by retinoic acid treatment. In contrast, cotransfection of TFIIB and IRF-1 into NIH 3T3 cells resulted in a dose-dependent repression of promoter activation which occurred in a TATA-dependent manner. Our results indicate the presence of a cell type-specific factor that mediates the functional interaction between IRFs and TFIIB and that acts in conjunction with the requirement of TATA and Inr for promoter activation.

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  1. [42]42. Maniatis, T., L. Whittemore, W. Du, C. Fan, A. D. Keller, V. J. Palombella, and D. N. Thanos. 1992. Positive and negative control of interferonb gene expression, p. 1193-1220. In S. L. McKnight and K. R. Yamamoto (ed.), Transcription regulation. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

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Authors
Wang, I.-M., Blanco, J. C. G., Tsai, S. Y., Tsai, M.-J., & Ozato, K.
Affiliations
National Institutes of Health (US)
Venue
Molecular and Cellular Biology
Published
1996-11-01
Volume
16
Issue
11
Pages
6313-6324
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2144093304
Cited by
64
References
72
Citations by year
2025: 1 · 2022: 1 · 2020: 1 · 2014: 1 · 2012: 1
FWCI
2.89
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interferon regulatory factors, IRF1, IRF2, TFIIB, interferon-stimulated response element, transcriptional regulation, protein-protein interaction, basal transcription machinery, TATA box, retinoic acid differentiation, P19 embryonal carcinoma cells, NIH3T3 cells
MeSH terms
Animals, Base Sequence, Binding Sites, Cell Differentiation, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Kinetics, Luciferases, Models, Biological, Phosphoproteins, Promoter Regions, Genetic, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Tretinoin, Tumor Cells, Cultured, Trans-Activators, Gene Expression Regulation, Viral, TATA Box, 3T3 Cells, Genes, Reporter, Carcinoma, Embryonal, Transcription Factor TFIIB, Interferon Regulatory Factor-2, Interferon Regulatory Factor-1, Mice

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