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

Nature Cell Biology volume 4, pages 140–147 (2002)Cite this article

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 TAFII130 potentiates STAT2 function, but TAFII28 or the HAT activity of TAFII250 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.

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Figure 1: IFN-induced histone acetylation in vivo correlates with STAT2 binding.
Figure 2: GCN5 recruitment site on STAT2 is required for transcriptional activity.
Figure 3: TAF requirements for ISG induction.
Figure 4: TBP is not required for IFN-stimulated transcription.
Figure 5: ISG expression is resistant to poliovirus 3Cpro protease.
Figure 6: Model of classical and IFN-stimulated transcriptional initiation in the presence of TBP degradation by viral proteases.

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Acknowledgements

We thank Y. Nakatani, R. Schiltz, S. Roth, M. Rosenfeld, P. Sarnow, C. Basilico, M. Garabedian, M. Pagano, O. Silvennoinen, P. Lengyel, A. García-Sastre, G. Stark, and N. Hernandez for the kind gifts of antibodies, cell lines, virus, plasmids, and primers, and for helpful advice and discussions. We particularly thank K.Gustin for the gift of poliovirus, and W. Xu for providing GCN5 before publication. We thank I. Rogatsky for primer sequences for the collagenase I promoter, M. Pagano for the primers for p27Kip1, M. Wathelet and D. Dean for helpful advice on ChIP assays, and K. Murphy for helpful comments. C. P. was supported by a Medical Scientist Training Grant (5T32GM03708) from the National Institutes of Health. This work was supported in part by research grants from the NIH (AI28900, AI46503, AI48204) and the American Heart Association (9951033T).

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  1. Matthew Paulson

    Present address: Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

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  1. Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, 10016, New York, USA

    Matthew Paulson, Carolyn Press, Eric Smith & David E. Levy

  2. Department of Microbiology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, 10016, New York, USA

    Naoko Tanese

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Correspondence to David E. Levy.

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Paulson, M., Press, C., Smith, E. et al. IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. Nat Cell Biol 4, 140–147 (2002). https://doi.org/10.1038/ncb747

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