Temporal lobe epilepsy: a unique window into living human brain epigenetic gene regulation

This scientific commentary refers to ‘Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy’ by Miller-Delaney et al. (10.1093/brain/awu373). Epigenetic modification of the genome is a powerful mechanism for regulation of RNA expression. For the large majority of non-neoplastic brain disorders, a lack of human brain tissue suitable for complementary epigenetic and RNA expression analyses poses a major challenge for translating data from experimental models to human disease. Temporal lobe epilepsy is a unique exception. Tissue from pharmacoresistant patients who undergo epilepsy surgery allow singular access for comprehensive molecular genetic studies. In this issue of Brain , Miller-Delaney and colleagues use this intriguing resource to report fundamental new insights into epigenetic regulation in human brain tissue (Miller-Delaney et al. , 2014).Epigenetic dynamics under disease conditions are generally thought to represent wide-scale alterations in the expression of multiple classes of RNA. In the context of epilepsy, however, most studies of epigenetic modifications have focused on distinct structural changes and alterations in the expression of specific mRNAs (Kobow et al. , 2009; Ryley Parrish et al. , 2013). Much less is known about genome-wide epigenetic alterations and corresponding patterns of RNA expression in the disease. Miller-Delaney and colleagues addressed the challenge of molecular genetic analyses in human brain tissue by comparing genome-wide DNA methylation patterns in the hippocampi of patients with pharmaco-refractory temporal lobe epilepsy with those in autopsy samples of brain tissue from individuals with non-neurological causes of …