Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities

Cell & Bioscience

Keji Zhao²  Zhiying Zhang¹  Kairong Cui²  Gang Ren² 

[1] College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, PR China;Systems Biology Center, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda 20892, MD, USA

关键词: Antiviral activities;    Transcription;    ChIP;    BRG1;    IRF2;    IRF1;   

Others  :  1220354
DOI  :  10.1186/s13578-015-0007-0

 received in 2015-03-12, accepted in 2015-03-27,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Ren et al.; licensee BioMed Central.

【 图 表 】

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