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Immunity. 2015 Apr 21;42(4):613-26. doi: 10.1016/j.immuni.2015.03.005. Epub 2015 Apr 7.

The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells.

Author information

1
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA.
2
State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou 510275, China.
3
Institute for Immunology, Tsinghua University, Beijing 100084, China.
4
Institute for Systems Biology, Seattle, WA 98109, USA.
5
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA.
6
Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
7
Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
8
State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: weil9@mail.sysu.edu.cn.
9
Institute for Immunology, Tsinghua University, Beijing 100084, China. Electronic address: chendong@tsinghua.edu.cn.

Erratum in

  • Immunity. 2015 Jun 16;42(6):1214.

Abstract

Epigenetic regulation of lineage-specific genes is important for the differentiation and function of T cells. Ten-eleven translocation (Tet) proteins catalyze 5-methylcytosine (5 mC) conversion to 5-hydroxymethylcytosine (5 hmC) to mediate DNA demethylation. However, the roles of Tet proteins in the immune response are unknown. Here, we characterized the genome-wide distribution of 5 hmC in CD4(+) T cells and found that 5 hmC marks putative regulatory elements in signature genes associated with effector cell differentiation. Moreover, Tet2 protein was recruited to 5 hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of Tet2 in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the control of cytokine gene expression in autoimmune disease. Collectively, our findings suggest that Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells.

PMID:
25862091
PMCID:
PMC4956728
DOI:
10.1016/j.immuni.2015.03.005
[Indexed for MEDLINE]
Free PMC Article

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