title: Bromodomain protein Brd3 promotes Ifnb1 transcription via enhancing IRF3/p300 complex formation and recruitment to Ifnb1 promoter in macrophages.
abstract: As members of bromodomain and extra-terminal motif protein family, bromodomain-containing proteins regulate a wide range of biological processes including protein scaffolding, mitosis, cell cycle progression and transcriptional regulation. The function of these bromodomain proteins (Brds) in innate immune response has been reported but the role of Brd3 remains unclear. Here we find that virus infection significantly downregulate Brd3 expression in macrophages and Brd3 knockout inhibits virus-triggered IFN-β production. Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection. Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production. Therefore, our work indicated that Brd3 may act as a coactivator in IRF3/p300 transcriptional activation of Ifnb1 and provided new epigenetic mechanistic insight into the efficient activation of the innate immune response.
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ren
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.
authors.forename: Qinlan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
authors.forename: Donghao
authors.initials: D
authors.lastname: Sun
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Han
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.|Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
mesh_terms: D000107:Acetylation; D000818:Animals; D064113:CRISPR-Cas Systems / Q000235:genetics; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014780:Viruses / Q000472:pathogenicity; D000092468:Bromodomain Containing Proteins
chemical_list: D050881:E1A-Associated p300 Protein; D006657:Histones; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C518476:Brd3 protein, mouse; D000092468:Bromodomain Containing Proteins; C494233:Irf3 protein, mouse; C494361:Ep300 protein, mouse