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Death domain-associated protein 6 (Daxx) selectively represses IL-6 transcription through histone deacetylase 1 (HDAC1)-mediated histone deacetylation in macrophages.

Authors
  • Yao, Zhenyu
  • Zhang, Qian
  • Li, Xia
  • Zhao, Dezhi
  • Liu, Yiqi
  • Zhao, Kai
  • Liu, Yin
  • Wang, Chunmei
  • Jiang, Minghong
  • Li, Nan
  • Cao, Xuetao
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Mar 28, 2014
Volume
289
Issue
13
Pages
9372–9379
Identifiers
DOI: 10.1074/jbc.M113.533992
PMID: 24550390
Source
Medline
Keywords
License
Unknown

Abstract

As a multifunctional nuclear protein, death domain-associated protein 6 (Daxx) regulates a wide range of biological processes, including cell apoptosis and gene transcription. However, the function of Daxx in innate immunity remains unclear. In our study, we show that Daxx is highly expressed in macrophages and localized in nucleus of macrophages. The expression of Daxx is significantly up-regulated by stimulation with TLR ligands LPS and poly(I:C). Silence of Daxx selectively represses IL-6 expression at transcription level in LPS-activated macrophages. Upon stimulation of LPS, Daxx specifically binds to the promoter of IL-6 and inhibits histone acetylation at IL-6 promoter region. Further mechanism analyses show that histone deacetylase 1 (HDAC1) interacts with Daxx and binds to the promoter of IL-6. Daxx silencing decreases the association of HDAC1 to IL-6 promoter. Therefore, our data reveal that Daxx selectively represses IL-6 transcription through HDAC1-mediated histone deacetylation in LPS-induced macrophages, acting as a negative regulator of IL-6 during innate immunity and potentially preventing inflammatory response because of overproduction of IL-6.

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