VIRUS-INFECTION INDUCES THE ASSEMBLY OF COORDINATELY ACTIVATED TRANSCRIPTION FACTORS ON THE IFN-BETA ENHANCER IN-VIVO

We have identified a virus-activated factor (VAF) that binds to a regu latory element shared by different virus-inducible genes. We provide e vidence that VAF contains two members of the interferon regulatory fac tor (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, bind s 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 includ es ATF-S/c-Jun and NF-kappa B. These observations provide a unique exa mple of the coordinate activation of multiple transcriptional activato r proteins and their highly cooperative assembly into a transcriptiona l enhancer complex in vivo.