5-Hydroxymethylcytosine Localizes to Enhancer Elements and is Associated with Survival in Glioblastoma Patients

Authors

Kevin C. Johnson, Dartmouth College
E. Andres Houseman, Oregon State University
Jessica E. King, Dartmouth College
Katharine M. von Herrmann, Dartmouth College
Camilo E. Fadu, University of Virginia
Brock C. Christensen, Dartmouth CollegeFollow

Document Type

Article

Publication Date

11-25-2016

Publication Title

Nature Communications

Department

Geisel School of Medicine

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.

DOI

10.1038/ncomms13177

Dartmouth Digital Commons Citation

Johnson, Kevin C.; Houseman, E. Andres; King, Jessica E.; von Herrmann, Katharine M.; Fadu, Camilo E.; and Christensen, Brock C., "5-Hydroxymethylcytosine Localizes to Enhancer Elements and is Associated with Survival in Glioblastoma Patients" (2016). Dartmouth Scholarship. 2479.
https://digitalcommons.dartmouth.edu/facoa/2479