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EMBO J. 2014 Oct 16;33(20):2332-48. doi: 10.15252/embj.201488447. Epub 2014 Aug 8.

Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex.

Author information

1
Laboratory of Infection and Prevention Institute for Virus Research Kyoto University, Sakyo-ku Kyoto, Japan CREST JST, Sakyo-ku Kyoto, Japan Laboratory of Host Defense WPI Immunology Frontier Research Center (IFReC), Osaka University Suita, Osaka, Japan Research Institute for Microbial Diseases Osaka University, Suita Osaka, Japan.
2
Laboratory of Allergic Diseases Institute for Advanced Medical Sciences Hyogo College of Medicine, Suita Osaka, Japan.
3
Laboratory of Systems Immunology WPI Immunology Frontier Research Center (IFReC), Nishinomiya Hyogo, Japan.
4
Laboratory of Infection and Prevention Institute for Virus Research Kyoto University, Sakyo-ku Kyoto, Japan CREST JST, Sakyo-ku Kyoto, Japan.
5
IBMC UPR 9022 CNRS, Strasbourg Cedex, France.
6
Laboratory of Host Defense WPI Immunology Frontier Research Center (IFReC), Osaka University Suita, Osaka, Japan Research Institute for Microbial Diseases Osaka University, Suita Osaka, Japan.
7
Laboratory of Infection and Prevention Institute for Virus Research Kyoto University, Sakyo-ku Kyoto, Japan CREST JST, Sakyo-ku Kyoto, Japan Laboratory of Host Defense WPI Immunology Frontier Research Center (IFReC), Osaka University Suita, Osaka, Japan otake@virus.kyoto-u.ac.jp.

Abstract

Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.

KEYWORDS:

chromatin remodeling; cytokine; gene regulation; innate immunity; macrophages

PMID:
25107474
PMCID:
PMC4253523
DOI:
10.15252/embj.201488447
[Indexed for MEDLINE]
Free PMC Article

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