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Gcn5 and PCAF negatively regulate interferon‐β production through HAT ‐independent inhibition of TBK 1
Author(s) -
Jin Qihuang,
Zhuang Lenan,
Lai Binbin,
Wang Chaochen,
Li Wenqian,
Dolan Brian,
Lu Yue,
Wang Zhibin,
Zhao Keji,
Peng Weiqun,
Dent Sharon YR,
Ge Kai
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201438990
Subject(s) - pcaf , innate immune system , biology , histone , histone acetyltransferase , microbiology and biotechnology , immune system , gene , genetics
Viral infection triggers innate immune signaling, which in turn induces interferon‐β ( IFN ‐β) production to establish innate antiviral immunity. Previous studies showed that Gcn5 (Kat2a), a histone acetyltransferase ( HAT ) with partial functional redundancy with PCAF (Kat2b), and Gcn5/ PCAF ‐mediated histone H3K9 acetylation (H3K9ac) are enriched on the active IFNB gene promoter. However, whether Gcn5/ PCAF and H3K9ac regulate IFN ‐β production is unknown. Here, we show that Gcn5/ PCAF ‐mediated H3K9ac correlates well with, but is surprisingly dispensable for, the expression of endogenous IFNB and the vast majority of active genes in fibroblasts. Instead, Gcn5/ PCAF repress IFN ‐β production and innate antiviral immunity in several cell types in a HAT ‐independent and non‐transcriptional manner: by inhibiting the innate immune signaling kinase TBK 1 in the cytoplasm. Our results thus identify Gcn5 and PCAF as negative regulators of IFN ‐β production and innate immune signaling.