AUTHOR=Meller Robert , Pearson Andrea , Simon Roger P. TITLE=Dynamic Changes in DNA Methylation in Ischemic Tolerance JOURNAL=Frontiers in Neurology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2015.00102 DOI=10.3389/fneur.2015.00102 ISSN=1664-2295 ABSTRACT=

Epigenetic mediators of gene expression are hypothesized to regulate transcriptomic responses to preconditioning ischemia and ischemic tolerance. Here, we utilized a methyl-DNA enrichment protocol and sequencing (ChIP-seq) to identify patterns of DNA methylation in an established model of ischemic tolerance in neuronal cultures (oxygen and glucose deprivation: OGD). We observed an overall decrease in global DNA methylation at 4 h following preconditioning ischemia (30 min OGD), harmful ischemia (120 min OGD), and in ischemic tolerant neuronal cultures (30 min OGD, 24 h recovery, 120 min OGD). We detected a smaller cohort of hypermethylated regions following ischemic conditions, which were further analyzed revealing differential chromosomal localization of methylation, and a differential concentration of methylation on genomic regions. Together, these data show that the temporal profiles of DNA methylation with respect to chromatin hyper- and hypo-methylation following various ischemic conditions are highly dynamic, and may reveal novel targets for neuroprotection.