title: Impairment of interferon-induced IRF-7 gene expression due to inhibition of ISGF3 formation by trichostatin A.
abstract: Two members of the signal transducer and activator of transcription family, STAT1 and STAT2, form, together with interferon regulatory factor 9 (IRF-9), the ISGF3 complex that activates the expression of the interferon-stimulated genes (ISG). The ISGF3 complex also participates in the virus-induced alpha/beta interferon (IFN-alpha/beta) gene amplification cascade by up-regulating IRF-7 gene expression. Here, we show that treatment of cells with trichostatin A (TSA), a deacetylase inhibitor, inhibits the virus-induced activation of IFN-alpha/beta promoters and dramatically reduces the ability of different ISG promoters to respond to IFN stimulation. Impairment of IFN-alpha/beta and ISG expression by TSA in infected cells is due to the blockage of interferon-stimulated ISGF3 complex formation, which leads to the abolition of IRF-7 gene expression. We also show that the TSA-dependent inhibition of ISGF3 is related to impaired nuclear accumulation of STAT2. Our data suggest that an acetylation/deacetylation mechanism participates in the regulation of cellular distribution and function of STAT2 in IFN-alpha/beta signaling.
authors.affiliation: UPR 2228-CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Pères, Université Paris V, 75270 Paris Cedex 06, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Génin
authors.forename: Pierre
authors.initials: P
authors.lastname: Morin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Civas
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006877:Hydroxamic Acids / Q000494:pharmacology*; D050839:Interferon Regulatory Factor-7; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D051379:Mice; D009522:Newcastle disease virus / Q000276:immunology / Q000472:pathogenicity; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D050839:Interferon Regulatory Factor-7; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; C494235:Irf7 protein, mouse; C494228:Isgf3g protein, mouse; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C012589:trichostatin A; D016899:Interferon-beta