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Nat Commun. 2016 Nov 25;7:13177. doi: 10.1038/ncomms13177.

5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients.

Author information

1
Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
2
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
3
Department of Biostatistics, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
4
Department of Neurology, University of Virginia, Charlottesville, Virginia 22908, USA.

Abstract

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and binding sites of transcription factors that drive cellular proliferation. In addition, model-based clustering results indicate that patients with low-5-hydroxymethylcytosine patterns have significantly poorer overall survival. Our results demonstrate that 5-hydroxymethylcytosine patterns are strongly related with transcription, localizes to disease-critical genes and are associated with patient prognosis.

PMID:
27886174
PMCID:
PMC5133638
DOI:
10.1038/ncomms13177
[Indexed for MEDLINE]
Free PMC Article

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