CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation

Wenqiang Cao, Jing Guo, Xiaofeng Wen, Li Miao, Feng Lin, Guanxin Xu, Ruoyu Ma, Shengxia Yin, Zhaoyuan Hui, Tingting Chen, Shixin Guo, Wei Chen, Yingying Huang, Yizhi Liu, Jianli Wang, Lai Wei () and Lie Wang ()
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Wenqiang Cao: Institute of Immunology, Zhejiang University School of Medicine
Jing Guo: Institute of Immunology, Zhejiang University School of Medicine
Xiaofeng Wen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Li Miao: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Feng Lin: Institute of Immunology, Zhejiang University School of Medicine
Guanxin Xu: Institute of Immunology, Zhejiang University School of Medicine
Ruoyu Ma: Institute of Immunology, Zhejiang University School of Medicine
Shengxia Yin: Institute of Immunology, Zhejiang University School of Medicine
Zhaoyuan Hui: Institute of Immunology, Zhejiang University School of Medicine
Tingting Chen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Shixin Guo: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Wei Chen: University of Pittsburgh
Yingying Huang: Core Facilities, College of Medicine, Zhejiang University
Yizhi Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Jianli Wang: Institute of Immunology, Zhejiang University School of Medicine
Lai Wei: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
Lie Wang: Institute of Immunology, Zhejiang University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11687

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