Other
14 Authors
- Wang X,
- Deng Y,
- Dong C,
- Aifantis I,
- Zou Y,
- Chen T,
- Yan X,
- Tanaka S,
- Tian Q,
- Zheng P,
- Kim BS,
- Ndiaye-Lobry D,
- Ichiyama K,
- Wei L
First Author | Ichiyama K | Year | 2015 |
Journal | Immunity | Volume | 42 |
Issue | 4 | Pages | 613-26 |
PubMed ID | 25862091 | Mgi Jnum | J:229699 |
Mgi Id | MGI:5753015 | Doi | 10.1016/j.immuni.2015.03.005 |
Citation | Ichiyama K, et al. (2015) The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells. Immunity 42(4):613-26 |
abstractText | 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. |