Effects of dynamic cytosine methylation on alternative pre-mRNA splicing in T lymphocytes. Homo sapiens

Intragenic 5-methylcytosine and CTCF mediate opposing affects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion. However, the mechanisms governing dynamic DNA methylation at CTCF binding sites were unclear. In this study, we identify the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF-mediated alternative splicing through conversion of 5-methylcytosine to its oxidation derivatives. Overall design: Transcriptional profiling of human T-lymphocytes in the naïve and activated states was performed by RNA-Seq. Methylation status (5mC and 5hmC) was assayed by medIP-Seq. CTCF binding sites were identified by ChIP-Seq.