Regulation of T cell cytokine expression by Tet2-mediated DNA demethylation [gene expression]

ABSTRACT: T cell function is regulated by epigenetic mechanisms. 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) proteins was identified to mediate DNA demethylation. Here, we characterize the genome-wide distribution of 5hmC in T cells using DNA immunoprecipitation coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with effector cell differentiation in the putative regulatory elements. Moreover, Tet2 protein is recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of the Tet2 gene in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the expression of cytokine genes. Collectively, our findings for the first time demonstrate a key role of Tet-mediated active DNA demethylation in T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE66944 | GEO | 2015/04/12

SECONDARY ACCESSION(S): PRJNA278448

REPOSITORIES: GEO