title: IFN consensus 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.
authors.affiliation: Department of Food Engineering & Biotechnology, Technion, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Weisz
authors.forename: S
authors.initials: S
authors.lastname: Kirchhoff
authors.forename: B Z
authors.initials: BZ
authors.lastname: Levi
mesh_terms: D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D007372:Interferons / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection / Q000235:genetics; D000099185:Interferon Regulatory Factor-8
chemical_list: D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D015500:Chloramphenicol O-Acetyltransferase; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D007372:Interferons; D010750:Phosphoproteins; D011070:Poly I-C; D012330:RNA, Double-Stranded; D012097:Repressor Proteins; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C494257:IRF1 protein, human