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

Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. von Herrmann, Camilo E. Fadul and Brock C. Christensen ()
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Kevin C. Johnson: Geisel School of Medicine at Dartmouth
E. Andres Houseman: College of Public Health and Human Sciences, Oregon State University
Jessica E. King: Geisel School of Medicine at Dartmouth
Katharine M. von Herrmann: Geisel School of Medicine at Dartmouth
Camilo E. Fadul: University of Virginia
Brock C. Christensen: Geisel School of Medicine at Dartmouth

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13177

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