Gcn5 and PCAF negatively regulate interferon-? production through HAT-independent inhibition of TBK1.

ABSTRACT: 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.

SUBMITTER: Jin Q 

PROVIDER: S-EPMC4253493 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature