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The promoter of IL-18 binding protein: Activation by an IFN-γ-induced complex of IFN regulatory factor 1 and CCAAT/enhancer binding protein β
- Source :
- Proceedings of the National Academy of Sciences. 99:16957-16962
- Publication Year :
- 2002
- Publisher :
- Proceedings of the National Academy of Sciences, 2002.
-
Abstract
- The IL-18 binding protein (IL-18BP) is a circulating inhibitor of the proinflammatory cytokine IL-18. It is constitutively expressed in mononuclear cells, and elevated expression is induced by IFN-γ. In this study, we characterized the IL-18BP promoter. We first showed that induction is at the transcriptional level and requiresde novoprotein synthesis. The IL-18BP promoter resides within 1.6 kb DNA upstream of the first exon and includes at least six regulatory elements. We identified in the basal promoter a gamma-activated sequence (GAS) proximal to the transcription start site (base 1), followed by an IFN regulatory factor 1 response element (IRF-E) and two CCAAT/enhancer binding protein β (C/EBPβ) sites, all of which are essential for basal promoter activity. Furthermore, GAS and IRF-E were essential for IFN-γ-induced transcription. Indeed, sera of IRF-1-deficient mice lacked basal and IFN-γ-induced IL-18BP. We found that after induction of IRF-1 by IFN-γ, it formed a complex with C/EBPβ, which bound to the IRF-E and GAS-containing proximal DNA. In contrast, the IFN-γ-induced signal transducer and activator of transcription 1 dimer did not associate with this GAS. In addition, we identified a silencer element and a distal enhancer at bases −1081 to −1272, which was also physically associated with IRF-1. The IRF-1–C/EBPβ complex described here probably plays a fundamental role in regulating additional IFN-γ-responsive genes.
- Subjects :
- Multidisciplinary
Transcription, Genetic
Ccaat-enhancer-binding proteins
CCAAT-Enhancer-Binding Protein-beta
Binding protein
Response element
CAAT box
Biological Sciences
Biology
Phosphoproteins
Molecular biology
DNA-Binding Proteins
Interferon-gamma
Upstream activating sequence
Enhancer Elements, Genetic
IRF1
Gene Expression Regulation
Transcription (biology)
Enhancer binding
Humans
Intercellular Signaling Peptides and Proteins
Promoter Regions, Genetic
Glycoproteins
Interferon Regulatory Factor-1
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....dd0e46e3424b49fa922033d3d00a1da9