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Gcn5 and PCAF negatively regulate interferon-? production through HAT-independent inhibition of TBK1 #MMPMID25269644
Jin Q; Zhuang L; Lai B; Wang C; Li W; Dolan B; Lu Y; Wang Z; Zhao K; Peng W; Dent SY; Ge K
EMBO Rep 2014[Nov]; 15 (11): 1192-201 PMID25269644show ga
Viral infection triggers innate immune signaling, which in turn induces interferon-? (IFN-?) 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-? 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-? production and innate antiviral immunity in several cell types in a HAT-independent and non-transcriptional manner: by inhibiting the innate immune signaling kinase TBK1 in the cytoplasm. Our results thus identify Gcn5 and PCAF as negative regulators of IFN-? production and innate immune signaling.