title: Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-γ-induced gene expression.
abstract: Signal transducers and activators of transcription (STATs) and interferon regulatory factors (IRFs) share common target genes. Here we show that the Irf7 gene is regulated by transcription factors STAT1 and IRF9 in response to the type II interferon (IFN) IFN-γ. IRF7 cooperated with STAT1 and IRF1 to stimulate the expression of a subset of IFN-γ-induced STAT1 target genes. IRF7-mediated control of the Gbp2 gene required the presence and basal activity of the S/T kinase TANK-binding kinase 1 (TBK1), whereas the binding of IRF7 to the Gbp2 promoter did not. Analysis of RNA polymerase II (Pol II) recruitment to the Gbp2 promoter revealed a role for IRF7 at later stages of the IFN-γ response. In support of the role of IRF7 in establishing an effective antibacterial response, IFN-γ-pretreated Irf7(-/-) macrophages showed an increased bacterial burden after infection with Listeria monocytogenes. Our data thus describe a biologically relevant basal activity of TBK1 and identify IRF7 as a novel player in the IFN-γ response.
authors.affiliation: Max F. Perutz Laboratories, Department of Genetics, Microbiology and Immunobiology, University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Farlik
authors.forename: Birgit
authors.initials: B
authors.lastname: Rapp
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marie
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Jamieson
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1 / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000737:chemistry / Q000235:genetics*; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D017434:Protein Structure, Tertiary; D050794:STAT1 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; C494258:Irf1 protein, mouse; C494235:Irf7 protein, mouse; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; C452200:Gbp2 protein, mouse