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

ABSTRACT: 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. Transcriptional profiling of human T-lymphocytes in the naÃ¯ve 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.

ORGANISM(S): Homo sapiens

SUBMITTER: David Sturgill

PROVIDER: E-GEOD-74850 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing.

Marina Ryan J RJ Sturgill David D Bailly Marc A MA Thenoz Morgan M Varma Garima G Prigge Maria F MF Nanan Kyster K KK Shukla Sanjeev S Haque Nazmul N Oberdoerffer Shalini S

The EMBO journal 20151228 3

Intragenic 5-methylcytosine and CTCF mediate opposing effects 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. Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF-mediated alternative splicing through conversion of 5-methylcytosine to its oxidatio ...[more]

PMID: 26711177

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