Gcn 5 and PCAF negatively regulate interferon-β production through HAT-independent inhibition of TBK1

Qihuang Jin, Lenan Zhuang, Binbin Lai, Chaochen Wang, Wenqian Li, Brian Dolan, Yue Lu, Zhibin Wang, Keji Zhao, Weiqun Peng, Sharon Y.R. Dent, Kai Ge

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 H3 K9ac 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 TBK1 in the cytoplasm. Our results thus identify Gcn5 and PCAF as negative regulators of IFN-β production and innate immune signaling.

Original languageEnglish (US)
Pages (from-to)1192-1201
Number of pages10
JournalEMBO Reports
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Gcn5/PCAF
  • H3K9ac
  • Innate immune signaling
  • Interferon-β
  • TBK1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Jin, Q., Zhuang, L., Lai, B., Wang, C., Li, W., Dolan, B., Lu, Y., Wang, Z., Zhao, K., Peng, W., Dent, S. Y. R., & Ge, K. (2014). Gcn 5 and PCAF negatively regulate interferon-β production through HAT-independent inhibition of TBK1. EMBO Reports, 15(11), 1192-1201. https://doi.org/10.15252/embr.201438990