title: The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.
abstract: Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter through activity at transcription factor AP-1-like sites. Interferon elicitors recruited the transcription factor IRF3 to the promoter, whereupon MafB acted as a transcriptional antagonist, impairing the interaction of coactivators with IRF3. Mathematical modeling supported the view that prepositioning of MafB on the promoter allows the system to respond rapidly to fluctuations in IRF3 activity. Higher expression of MafB in human pancreatic islet beta cells might increase cellular vulnerability to viral infections associated with the etiology of type 1 diabetes.
authors.affiliation: Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Hwijin
authors.initials: H
authors.lastname: Kim
authors.forename: Brian
authors.initials: B
authors.lastname: Seed
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology*; D016899:Interferon-beta / Q000235:genetics; D051258:MafB Transcription Factor / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D011401:Promoter Regions, Genetic; D018808:Transcription Factor AP-1 / Q000276:immunology; D014158:Transcription, Genetic; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D051258:MafB Transcription Factor; D018808:Transcription Factor AP-1; D016899:Interferon-beta