title: TET3 Inhibits Type I IFN Production Independent of DNA Demethylation.
abstract: Type I interferons (IFNs) play both beneficial and harmful roles in antiviral responses. Precise regulation of host type I IFNs is thus needed to prevent immune dysregulation. Here, we find that the DNA demethylase TET3 is a negative regulator of IFN-β in response to poly(I:C) stimulation or viral infection. Deletion of TET3 enhances antiviral responses, with elevated expression of IFN-β and IFN-stimulated genes. The catalytic domain of TET3 was critical for the suppression of IFN-β production, but TET3 enzymatic activity was dispensable. Instead, the catalytic domain of TET3 interacts with HDAC1 and SIN3A, thus enhancing their binding to the Ifnb1 promoter. Our study demonstrates that TET3 negatively regulates type I IFN production independent of DNA demethylation. This not only sheds light on TET3 as a signaling protein in immune cells for gene regulation but also will help to develop strategies to prevent type I IFN-related disease.
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Xue
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: hongyanwang@sibcb.ac.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000073398:Demethylation; D049308:Dioxygenases; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D011070:Poly I-C / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014777:Virus Diseases / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000611649:IFNG protein, mouse; D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D016899:Interferon-beta; D007371:Interferon-gamma; D004247:DNA; D049308:Dioxygenases; C551915:Tet3 protein, mouse; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D011070:Poly I-C