IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff

Nat Cell Biol. 2002 Feb;4(2):140-7. doi: 10.1038/ncb747.

Abstract

Type I interferon (IFN) stimulates transcription through a heteromeric transcription factor that contains tyrosine-phosphorylated STAT2. We show that STAT2 recruits histone acetyltransferases (HAT) through its transactivation domain, resulting in localized transient acetylation of histones. GCN5, but not p300/CBP or PCAF, is required for STAT2 function. However, GCN5 function is impaired by the transcriptional antagonist, adenovirus E1A oncoprotein. The TFIID component TAF(II)130 potentiates STAT2 function, but TAF(II)28 or the HAT activity of TAF(II)250 do not, and transcriptional induction can proceed independently of the TATA-binding protein, TBP. Moreover, IFN-stimulated transcription was resistant to poliovirus-targeted degradation by TBP, and continued despite host-cell transcriptional shutoff during poliovirus infection. We conclude that a non-classical transcriptional mechanism combats an anticellular action of poliovirus, through a TBP-free TAF-containing complex and GCN5.

Publication types

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

MeSH terms

  • Acetyltransferases / metabolism*
  • Adenovirus E1A Proteins / metabolism
  • Animals
  • Cell Cycle Proteins
  • Cell Line
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • Histone Acetyltransferases
  • Histones / metabolism
  • Humans
  • Interferon Type I / metabolism*
  • Macromolecular Substances
  • Models, Genetic
  • Poliovirus / genetics
  • Poliovirus / metabolism*
  • Protein Binding
  • STAT2 Transcription Factor
  • Saccharomyces cerevisiae Proteins*
  • TATA-Binding Protein Associated Factors*
  • TATA-Box Binding Protein
  • Trans-Activators / metabolism*
  • Transcription Factor TFIID*
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology*
  • Viral Proteins / metabolism
  • p300-CBP Transcription Factors

Substances

  • Adenovirus E1A Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Histones
  • ISG-54 protein, human
  • Interferon Type I
  • Macromolecular Substances
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Saccharomyces cerevisiae Proteins
  • TAF1 protein, S cerevisiae
  • TAF4 protein, human
  • TATA-Binding Protein Associated Factors
  • TATA-Box Binding Protein
  • Trans-Activators
  • Transcription Factor TFIID
  • Transcription Factors
  • Viral Proteins
  • Acetyltransferases
  • Histone Acetyltransferases
  • KAT2A protein, human
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Cysteine Endopeptidases
  • 3C proteases