title: Reciprocal regulation of RORγt acetylation and function by p300 and HDAC1.
abstract: T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORγt) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORγt itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORγt at its K81 residue. Knockdown of p300 downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells. In addition, p300 can promote RORγt-mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORγt and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORγt, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORγt-mediated transcriptional activation of IL-17.
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032, China.|Department of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Qingsi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Nie
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Qijuan
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zuojia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lv
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Andy
authors.initials: A
authors.lastname: Tsun
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032, China.|Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Jijia
authors.initials: J
authors.lastname: Shen
authors.affiliation: Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050881:E1A-Associated p300 Protein; D056284:Histone Deacetylase 1