The Methylcytosine Dioxygenase Tet2 Promotes DNA Demethylation and Activation of Cytokine Gene Expression in T Cells

Kenji Ichiyama, Tingting Chen, Xiaohu Wang, Xiaowei Yan, Byung Seok Kim, Shinya Tanaka, Delphine Ndiaye-Lobry, Yuhua Deng, Yanli Zou, Pan Zheng, Qiang Tian, Iannis Aifantis, Lai Wei, Chen Dong

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)613-626
Number of pages14
JournalImmunity
Volume42
Issue number4
DOIs
Publication statusPublished - Apr 21 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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