The Chromatin-Remodeling BAF Complex Mediates Cellular Antiviral Activities by Promoter Priming

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 06/2004; 24(10):4476-86. DOI: 10.1128/MCB.24.10.4476-4486.2004
Source: PubMed


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-α) 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-α 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.

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