title: Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities.
abstract: BACKGROUND
  Cellular antiviral activities are critically controlled by transcriptional activation of interferon-inducible genes, involving interferon regulatory factors (IRFs). Previous data suggested that IRF1 is an activator and IRF2 is a repressor, which functionally antagonize each other in transcriptional regulation. However, it is not clear how these two factors function to regulate cellular antiviral activities.
  
  
  RESULTS
  We show that IRF2 is critically required for the induction of the TLR3 and other interferon-inducible genes in a chromatin environment. While both IRF1 and IRF2 directly interact with the BAF chromatin remodeling complex, IRF2 is associated with the TLR3 promoter in the unstimulated state and IRF1 binding to the promoter is strongly induced by stimulation with interferon, suggesting that these two factors may function at different stages of gene induction in the recruitment of the BAF complex. IRF2 acts to maintain the basal level expression, an open chromatin structure, and active histone modification marks (H3K9, K14 acetylation and H3K4 tri-methylation) of the TLR3 promoter in the unstimulated state, while IRF1 serves to rapidly activate the promoter upon stimulation.
  
  
  CONCLUSIONS
  IRF1 and IRF2 of the IRF family of transcription factors play distinct roles in cellular response to viral infection. IRF2 binds to TLR3 and other IFN-inducible gene promoters and maintains an active chromatin structure in the unstimulated state, which is required for their induction, while IRF1 binding to these promoters activates their transcription upon viral infection. Thus, the division of labor between the IRF transcription factor family members plays a pivotal role in coordinating the transcriptional activation in the cellular antiviral response.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100 PR China.|Systems Biology Center, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Systems Biology Center, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100 PR China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Systems Biology Center, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
keywords: Antiviral activities; BRG1; ChIP; IRF1; IRF2; Transcription