Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to
DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic
epilepsy. Here, through methylation analysis of all annotated C-
phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of
temporal lobe epilepsy with or without
hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive
non-coding RNA in human
temporal lobe epilepsy. A total of 146
protein-coding genes exhibited altered DNA methylation in
temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in
temporal lobe epilepsy with or without
hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild
hippocampal sclerosis). In addition to genes associated with neuronal,
neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in
temporal lobe epilepsy, but overall few genes previously associated with
epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive
microRNA were identified in
temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of
long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human
temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain.