The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming.

  • Cui K
  • Tailor P
  • Liu H
 et al. 
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Abstract

The elicitation of cellular antiviral activities is dependent on the rapid transcriptional activation of interferon (IFN) target genes. It is not clear how the interferon target promoters, which are organized into chromatin structures in cells, rapidly respond to interferon or viral stimulation. In this report, we show that alpha IFN (IFN-alpha) treatment of HeLa cells induced hundreds of genes. The induction of the majority of these genes was inhibited when one critical subunit of the chromatin-remodeling SWI/SNF-like BAF complexes, BAF47, was knocked down via RNA interference. Inhibition of BAF47 blocked the cellular response to viral infection and impaired cellular antiviral activity by inhibiting many IFN- and virus-inducible genes. We show that the BAF complex was required to mediate both the basal-level expression and the rapid induction of the antiviral genes. Further analyses indicated that the BAF complex primed some IFN target promoters by utilizing ATP-derived energy to maintain the chromatin in a constitutively open conformation, allowing faster and more potent induction after IFN-alpha treatment. We propose that constitutive binding of the BAF complex is an important mechanism for the IFN-inducible promoters to respond rapidly to IFN and virus stimulation.

Author-supplied keywords

  • Antigens, Differentiation
  • Antiviral Agents
  • Antiviral Agents: metabolism
  • Base Sequence
  • Cell Line
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Chromatin: metabolism
  • Chromosomal Proteins, Non-Histone
  • DNA Helicases
  • DNA Primers
  • DNA Primers: genetics
  • DNA-Binding Proteins
  • DNA-Binding Proteins: genetics
  • DNA-Binding Proteins: metabolism
  • HeLa Cells
  • Humans
  • Interferon Type I
  • Interferon Type I: pharmacology
  • Membrane Proteins
  • Membrane Proteins: genetics
  • Models, Biological
  • Newcastle disease virus
  • Newcastle disease virus: pathogenicity
  • Nuclear Proteins
  • Nuclear Proteins: metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering
  • RNA, Small Interfering: genetics
  • Recombinant Proteins
  • Signal Transduction
  • Transcription Factors
  • Transcription Factors: metabolism

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Authors

  • Kairong Cui

  • Prafullakumar Tailor

  • Hong Liu

  • Xin Chen

  • Keiko Ozato

  • Keji Zhao

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