title: Dynamic changes in DNA methylation in ischemic tolerance.
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.
authors.affiliation: Translational Stroke Program, Neuroscience Institute, Morehouse School of Medicine , Atlanta, GA , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Meller
authors.affiliation: Translational Stroke Program, Neuroscience Institute, Morehouse School of Medicine , Atlanta, GA , USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pearson
authors.affiliation: Translational Stroke Program, Neuroscience Institute, Morehouse School of Medicine , Atlanta, GA , USA ; Grady Memorial Hospital , Atlanta, GA , USA.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Simon
keywords: ChIP-seq; DNA methylation; ischemia; ischemic tolerance; preconditioning; stroke