IFN consenus sequence binding protein (ICSBP) is a conditional repressor of IFN inducible promoters
Abstract
IFN stimulated genes (ISGs) contain common DNA motif termed IFN consensus sequence (ICS) at their promoters that enable IFN responsiveness. Different transcription factors capable of interacting with the ICS have been described. Previously, we reported the cloning of a factor capable of binding to the ICS (ICSBP) that demonstrates similarity at DNA the binding domain with three other ICS binding factor, i.e. IRF-1, IRF-2 and ISGF3 gamma. ICSBP is expressed constitutively in hematopoietic cells and its expression is further induced by IFN-gamma. This is a negative trans-acting regulator of ISGs; however, its effect is attenuated following prolonged exposures of cells to both types of IFNs. In this communication, we show that short exposures of cells to IFNs (priming) are sufficient to alleviate ICSBP mediated repression. Further, exposure of primed cells to the synthetic dsRNA (polyl-polyC) results in total abrogation of ICSBP repression. In an attempt to unravel the molecular mechanism governing this conditional repression of ICSBP, the direct involvement of transcriptional activator IRF-1 is demonstrated. We postulate that constitutive expression of ICSBP in hematopoietic cells is mediating submaximal expression of ISGs such as MHC class I. Our data demonstrate that IRF-1 competes with ICSBP for the binding to the ISRE element, resulting in the alleviation of ICSBP repression. Thus, the magnitude of ISGs expression is a result of a fine balance between positive and negative regulators.
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ICSBP is a transcriptional repressor acting through the IFN-stimulated response element (ISRE).
“Subsequent studies have shown that ICSBP is a transcriptional repressor acting through the IFN-stimulated response element (ISRE). (6,20,21)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [21]
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- Authors
- Welsz, A., Kirchhoff, S., & Levi, B.-Z.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Helmholtz Centre for Infection Research (DE)
- Corresponding author
- Levi, Ben-Zion
- ORCID
- Levi, Ben-Zion
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1994
- Volume
- 6
- Issue
- 8
- Pages
- 1125-1131
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2155528120
- Cited by
- 50
- References
- 0
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IRF8, interferon-stimulated genes, IRF1, IRF2, transcriptional repression, interferon-gamma, double-stranded RNA, MHC class I expression, hematopoietic cells, transcription factor competition
- MeSH terms
- Interferon Regulatory Factor-8, Carrier Proteins, DNA-Binding Proteins, HeLa Cells, Humans, Interferons, Phosphoproteins, Poly I-C, Promoter Regions, Genetic, Repressor Proteins, RNA, Double-Stranded, Transcription Factors, Transfection, Chloramphenicol O-Acetyltransferase, Antisense Elements (Genetics), Interferon Regulatory Factors, Interferon Regulatory Factor-1
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