Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo

Mol Cell. 1998 Mar;1(4):507-18. doi: 10.1016/s1097-2765(00)80051-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activating Transcription Factor 2
  • Animals
  • Base Sequence
  • CHO Cells
  • CREB-Binding Protein
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Cricetinae
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic / physiology*
  • Fungal Proteins / genetics
  • Gene Expression Regulation, Viral
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon-beta / genetics*
  • Interferon-beta / metabolism
  • Leucine Zippers / physiology
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Nuclear Proteins / analysis
  • Phosphorylation
  • Recombinant Fusion Proteins / metabolism
  • Respirovirus / genetics*
  • Respirovirus / metabolism
  • Respirovirus Infections / genetics*
  • Respirovirus Infections / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators*
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / physiology*

Substances

  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • IRF3 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • NF-kappa B
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Interferon-beta
  • DNA
  • CREB-Binding Protein
  • CREBBP protein, human