Maximal induction of a subset of interferon target genes requires the chromatin-remodeling activity of the BAF complex.
The mammalian SWI/SNF-like chromatin-remodeling BAF complex plays several important roles in controlling cell proliferation and differentiation. Interferons (IFNs) are key mediators of cellular antiviral and antiproliferative activities. In this report, we demonstrate that the BAF complex is required for the maximal induction of a subset of IFN target genes by alpha IFN (IFN-alpha). The BAF complex is constitutively associated with the IFITM3 promoter in vivo and facilitates the chromatin remodeling of the promoter upon IFN-alpha induction. Furthermore, we show that the ubiquitous transcription activator Sp1 interacts with the BAF complex in vivo and augments the BAF-mediated activation of the IFITM3 promoter. Sp1 binds constitutively to the IFITM3 promoter in the absence of the BAF complex, suggesting that it may recruit and/or stabilize the BAF complex binding to the IFITM3 promoter. Our results bring new mechanistic insights into the antiproliferative effects of the chromatin-remodeling BAF complex.
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hong
H
Liu
Hyeog
H
Kang
Rui
R
Liu
Xin
X
Chen
Keji
K
Zhao
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism* / Q000502:physiology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D002843:Chromatin; D003432:Cross-Linking Reagents; D016898:Interferon-alpha; D009707:Nucleosomes; D009841:Oligonucleotides; D016329:Sp1 Transcription Factor; D007372:Interferons