Pluto Bioinformatics

GSE128951: 5-hydroxymethylcytosine Promotes Productive Transcription and Inhibits Spurious Promoters

Bulk RNA sequencing

Covalent DNA modifications play vital roles during animal development. While 5-methylcytosine (5mC) is important for imprinting, X chromosome inactivation and transcriptional repression, the function of 5-hydroxymethylcytosine (5hmC) is less well defined. Recent studies indicate that 5hmC can be stable and long-lived in some cell types, suggesting roles beyond a DNA demethylation intermediate. Here we show that oxidation of 5mC to 5hmC enhances transcription of a specific repertoire of genes. 5hmC upregulates transcription by counteracting the repressive effects of promoter-proximal 5mC, while supressing the ability of gene body resident spurious transcription initiation sites to produce mature transcripts. By contrast, the equivalent hypomethylation results in chaotic gene expression potentiating a broad collection of genes and cryptic promoters. Our observations provide an explanation why some post-mitotic cell types favour high 5hmC in the genomes, while equivalent global hypomethylation is rarely observed. SOURCE: Skirmantas Kriaucionis (skirmantas.kriaucionis@ludwig.ox.ac.uk) - Ludwig Institute for Cancer Research