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.
Highlights
The role and underlying mechanism of Daxx in innate immunity remain to be investigated
We found that histone deacetylase 1 (HDAC1) bound to the same region with Daxx in promoter of IL-6 in macrophages (Fig. 6C), and silencing Daxx decreased the association of HDAC1 to IL-6 promoter (Fig. 6D)
We have revealed that Daxx is a negative regulator of IL-6 during innate immune response
Summary
The role and underlying mechanism of Daxx in innate immunity remain to be investigated. Results: Daxx interacts with HDAC1 and binds to the promoter of IL-6. Daxx selectively represses IL-6 transcription through HDAC1-mediated histone deacetylation. Conclusion: Daxx selectively represses IL-6 transcription in TLR-triggered 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. Further mechanism analyses show that histone deacetylase 1 (HDAC1) interacts with Daxx and binds to the promoter of IL-6. 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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