Characterization of 5-hmC DNA Methylation Patterns in the Hippocampus of an Experimental Model of Epilepsy

Temporal lobe epilepsy is one of the most common refractory epilepsies in the world. Epilepsy progression is controlled through the expression of epilepsy permissive genes, ultimately resulting in a hyperexcitable network and spontaneous seizures. DNA methylation has been explored as a potential epigenetic regulatory mechanism of gene expression in epilepsy, however, the role of 5-hydroxymethylcytosine (5-hmC) has been underexplored to date. 5-hmC is a stable epigenetic mark most abundantly expressed in the brain. In this study, we show that 5-hmC but not 5-methylcytosine (5-mC) is lost in temporal lobe epilepsy. Using 5-hmC meDIP-sequencing, we characterized epileptic 5-hmC distribution in the rat kainic acid model of temporal lobe epilepsy. We identified the correlation of 5-hmC loss and gain with epilepsy-associated gene ontology pathways and implicate the potential involvement of multiple cell types with 5-hmC regulation of temporal lobe epilepsy. Overall, we show that 5-hmC has the potential to be a crucial regulator of epilepsy and epileptic gene expression and are the first to characterize the genomic distribution of 5-hmC in a model of epilepsy.