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 - 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 -