title: CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation.
abstract: T-cell development in the thymus is largely controlled by an epigenetic program, involving in both DNA methylation and histone modifications. Previous studies have identified Cxxc1 as a regulator of both cytosine methylation and histone 3 lysine 4 trimethylation (H3K4me3). However, it is unknown whether Cxxc1 plays a role in thymocyte development. Here we show that T-cell development in the thymus is severely impaired in Cxxc1-deficient mice. Furthermore, we identify genome-wide Cxxc1-binding sites and H3K4me3 modification sites in wild-type and Cxxc1-deficient thymocytes. Our results demonstrate that Cxxc1 directly controls the expression of key genes important for thymocyte survival such as RORγt and for T-cell receptor signalling including Zap70 and CD8, through maintaining the appropriate H3K4me3 on their promoters. Importantly, we show that RORγt, a direct target of Cxxc1, can rescue the survival defects in Cxxc1-deficient thymocytes. Our data strongly support a critical role of Cxxc1 in thymocyte development.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Cao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Miao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Guanxin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Ma
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Shengxia
authors.initials: S
authors.lastname: Yin
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Shixin
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.|Division of Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Core Facilities, College of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D060168:Thymocytes / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C501971:Cxxc1 protein, mouse; D006657:Histones; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators; C000626468:histone H3 trimethyl Lys4; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse