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

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
Externally publishedYes

Fingerprint

Histone Acetyltransferases
Interferons
Acetylation
Innate Immunity
Antiviral Agents
Genes
Virus Diseases
Fibroblasts
Histones
Redundancy
Cytoplasm
Phosphotransferases

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Cite this

Gcn 5 and PCAF negatively regulate interferon-β production through HAT-independent inhibition of TBK1. / Jin, Qihuang; Zhuang, Lenan; Lai, Binbin; Wang, Chaochen; Li, Wenqian; Dolan, Brian; Lu, Yue; Wang, Zhibin; Zhao, Keji; Peng, Weiqun; Dent, Sharon Y R; Ge, Kai.

In: EMBO Reports, Vol. 15, No. 11, 01.11.2014, p. 1192-1201.

Research output: Contribution to journalArticle

Jin, Q, Zhuang, L, Lai, B, Wang, C, Li, W, Dolan, B, Lu, Y, Wang, Z, Zhao, K, Peng, W, Dent, SYR & Ge, K 2014, 'Gcn 5 and PCAF negatively regulate interferon-β production through HAT-independent inhibition of TBK1', EMBO Reports, vol. 15, no. 11, pp. 1192-1201. https://doi.org/10.15252/embr.201438990
Jin, Qihuang ; Zhuang, Lenan ; Lai, Binbin ; Wang, Chaochen ; Li, Wenqian ; Dolan, Brian ; Lu, Yue ; Wang, Zhibin ; Zhao, Keji ; Peng, Weiqun ; Dent, Sharon Y R ; Ge, Kai. / Gcn 5 and PCAF negatively regulate interferon-β production through HAT-independent inhibition of TBK1. In: EMBO Reports. 2014 ; Vol. 15, No. 11. pp. 1192-1201.
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