title: Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo.
abstract: We have identified a virus-activated factor (VAF) that binds to a regulatory element shared by different virus-inducible genes. We provide evidence that VAF contains two members of the interferon regulatory factor (IRF) family of transcriptional activator proteins (IRF-3 and IRF-7), as well as the transcriptional coactivator proteins p300 and CBP. Remarkably, VAF, as well as recombinant IRF-3 and IRF-7 proteins, binds very weakly to the interferon-beta (IFN-beta) gene promoter in vitro. However, in virus-infected cells, both proteins are recruited to the endogenous IFN-beta promoter as part of a protein complex that includes ATF-2/c-Jun and NF-kappa B. These observations provide a unique example of the coordinate activation of multiple transcriptional activator proteins and their highly cooperative assembly into a transcriptional enhancer complex in vivo.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Wathelet
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: B S
authors.initials: BS
authors.lastname: Parekh
authors.forename: L V
authors.initials: LV
authors.lastname: Ronco
authors.forename: P M
authors.initials: PM
authors.lastname: Howley
authors.forename: T
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D050882:CREB-Binding Protein; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D016350:Leucine Zippers / Q000502:physiology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018108:Respirovirus / Q000235:genetics* / Q000378:metabolism; D010253:Respirovirus Infections / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C494232:IRF3 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016328:NF-kappa B; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016899:Interferon-beta; D004247:DNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human