IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff.
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.
Paulson
Matthew
M
Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Press
Carolyn
C
Smith
Eric
E
Tanese
Naoko
N
Levy
David E
DE
D000086042:3C Viral Proteases; D000123:Acetyltransferases / Q000378:metabolism*; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D046911:Macromolecular Substances; D008957:Models, Genetic; D017955:Poliovirus / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins; D050795:STAT2 Transcription Factor; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000086042:3C Viral Proteases; D000123:Acetyltransferases; D017500:Adenovirus E1A Proteins; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D007370:Interferon Type I; D046911:Macromolecular Substances; D016601:RNA-Binding Proteins; D050795:STAT2 Transcription Factor; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D014764:Viral Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C484289:IFIT2 protein, human; C494084:STAT2 protein, human; C106785:TAF1 protein, S cerevisiae; C101882:TAF4 protein, human; C501179:KAT2A protein, human