TY - JOUR
T1 - The Methylcytosine Dioxygenase Tet2 Promotes DNA Demethylation and Activation of Cytokine Gene Expression in T Cells
AU - Ichiyama, Kenji
AU - Chen, Tingting
AU - Wang, Xiaohu
AU - Yan, Xiaowei
AU - Kim, Byung Seok
AU - Tanaka, Shinya
AU - Ndiaye-Lobry, Delphine
AU - Deng, Yuhua
AU - Zou, Yanli
AU - Zheng, Pan
AU - Tian, Qiang
AU - Aifantis, Iannis
AU - Wei, Lai
AU - Dong, Chen
N1 - Funding Information:
We thank our colleagues for their help and suggestions. The work was supported in part by grants from NIH to C.D. (AR050772) and grants from National Basic Research Program of China (2013CB967001 and 2015CB964601) to L.W. K.I. receives JSPS postdoctoral fellowships for research abroad. C.D. is a Bayer Chair Professor at Tsinghua University.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/21
Y1 - 2015/4/21
N2 - Epigenetic regulation of lineage-specific genes is important for the differentiation and function of Tcells. Ten-eleven translocation (Tet) proteins catalyze 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) to mediate DNA demethylation. However, the roles of Tet proteins in the immune response are unknown. Here, we characterized the genome-wide distribution of 5hmC in CD4+ Tcells and found that 5hmC marks putative regulatory elements in signature genes associated with effector cell differentiation. Moreover, Tet2 protein was recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of Tet2 in Tcells decreased their cytokine expression, associated with reduced p300 recruitment. Invivo, 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 Tcells.
AB - Epigenetic regulation of lineage-specific genes is important for the differentiation and function of Tcells. Ten-eleven translocation (Tet) proteins catalyze 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) to mediate DNA demethylation. However, the roles of Tet proteins in the immune response are unknown. Here, we characterized the genome-wide distribution of 5hmC in CD4+ Tcells and found that 5hmC marks putative regulatory elements in signature genes associated with effector cell differentiation. Moreover, Tet2 protein was recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of Tet2 in Tcells decreased their cytokine expression, associated with reduced p300 recruitment. Invivo, 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 Tcells.
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U2 - 10.1016/j.immuni.2015.03.005
DO - 10.1016/j.immuni.2015.03.005
M3 - Article
C2 - 25862091
AN - SCOPUS:84928184771
SN - 1074-7613
VL - 42
SP - 613
EP - 626
JO - Immunity
JF - Immunity
IS - 4
ER -
