title: Death domain-associated protein 6 (Daxx) selectively represses IL-6 transcription through histone deacetylase 1 (HDAC1)-mediated histone deacetylation in macrophages.
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.
authors.affiliation: From the National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Dezhi
authors.initials: D
authors.lastname: Zhao
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: Minghong
authors.initials: M
authors.lastname: Jiang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D056970:Co-Repressor Proteins; D044127:Epigenesis, Genetic / Q000187:drug effects; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D006657:Histones; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D051193:Toll-Like Receptors; D056284:Histone Deacetylase 1
keywords: Daxx; Histone Acetylation; Histone Deacetylase; IL-6; Innate Immunity; Lipopolysaccharide (LPS); Macrophages; Toll-like Receptors (TLR)