Genome-wideBrain DNAMethylationandGeneExpression Patterns Unravel Epigenetic Reprogramming in Mesial Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common drug-resistant epilepsy in adults, characterized by hippocampus sclerosis. To date, the etiology of MTLE epileptogenesis and the molecular mechanisms underlying hippocampus sclerosis remain largely unclear. Altered genome-wide DNA methylation patterns and differential gene expression have been reported to be involved in the pathophysiological mechanism of epileptogenesis. To discover epigenetic reprogramming patterns associated with MTLE, we used a higher-throughput microarray, Illumina Infinium 850 K BeadChip, and RNA sequence to analyze epigenome-wide DNA methylation and related gene expressions. We also performed an enrichment analysis to find differences between the patients and autopsy controls. Through data analysis we identified 1832 DNA differentially methylated sites, and ten differentially methylated regions in several chromosomes. The differentially methylated genes were found enriched in "synaptic vesicle", "synaptic vesicle exocytosis", "regulation of synaptic plasticity", "Parkinson's disease", and "Oxidative phosphorylation". Correlation analysis of RNA expression and DNA methylation revealed that 16/48 genes' DNA methylation marks residing in the promoter region, and 32/48 were located within the gene body. These findings assist with a better understanding of the molecular pathogenesis of MTLE and aid in designing effective tailored interventions. Overall design: to better understand the molecular pathogenesis of MTLE and to aid in designing effective tailored interventions.