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Intragenic DNA methylation prevents cryptic transcription initiations on gene bodies [RNA-seq]

GSE72855 Mus musculus Expression profiling by high throughput sequencing 29 samples Submitted 2017/02/25 Platform GPL16173Platform GPL19057
Summary
In mammals, DNA methylation occurs mainly at 5mC of CpG dinucleotides. The methylation on the promoter leads to the suppression of gene expression, while the functional role of gene body DNA methylation in highly expressed genes has yet to be clarified. Here, we show that the Dnmt3b-dependent intragenic DNA methylation protects the gene body from RNA Polymerase II (RNA Pol II) spurious entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that loss of Dnmt3b leads to an increase of the RNA Pol II engagement within gene bodies and spurious intragenic transcription initiation events. Furthermore, inhibition of RNA Pol II spurious entry depends on the enzymatic activity of the Dnmt3b recruited by H3K36me3. Thus, elongating RNA Pol II triggers an epigenetic crosstalk that involves SetD2, H3K36me3, Dnmt3b, and DNA methylation to ensure gene transcription initiation fidelity with implications for intragenic hypomethylation in cancer.
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Direct links to NCBI, no account and no request form: the whole study as GSE72855_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 29 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA295210 and SRA study SRP063529. Searching any of these in the dataset finder brings you back here.

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