New Differentially Expressed Genes and Differential DNA Methylation Underlying Refractory Epilepsy

Over 65 million people are affected with epilepsy worldwide. A variety of genetic and environmental factors have been associated with epilepsy and seizures. In the case of epilepsy, DNA methylation has been deemed one of the principal epigenetic mechanisms leading to epilepsy. These affect genomic reprograming, tissue-specific gene expression and global gene silencing without affecting the sequence. 

It has been seen that many of these DNA methylations are present at the promoters of genes, resulting in a decrease of gene expression. Besides promotors, an inverse relationship between gene expression and DNA methylation has been seen in exons and introns. Not only has it been discovered that selective changes in genome-wide DNA methylation and increased DNA methyltransferase are associated with temporal lobe epilepsy (TLE), but also that ketogenic diets could attenuate seizure progression though DNA methylation. 

The work of Xi Liu et al. was focused on analyzing the pattern of genome wide DNA methylation and gene expression using methylated DNA immunoprecipitation linked with sequencing. As a result, they were able to distinguish a new pattern of DNA methylation associated with refractory epilepsy patients. They also found that there was no significant difference between epileptic samples and controls in genome, CpG, CHG, and CHH coverage distribution and that differentially methylated regions were discovered on all genes except for the male Y chromosome. Generally, no significant relationship in modulation was found between DNA methylation and gene expression. Xi Liu et al, also working towards generating DNA methylation and gene expression profiles to prove the relationship between DNA methylation and gene expression via distribution of hyper-, hypo- and unmethylated gene expression levels in different elements.

     The importance of this paper is that is the first genome wide report on DNA methylation and gene expression in refractory epilepsy patients. Over 62 differentially expressed genes were found to be correlated with epilepsy and seizures. However, the similarity in results between epileptic samples and the controls indicated no significant difference in global DNA methylation and gene expression. That is, the change in DNA methylation in the study is no corresponded with alterations in gene expression.

Reference: Liu, X., Ou, S., Xu, T., Liu, S. Yuan, J., Huang, Y., Qin, L., Yang, H., Chen, L., Tan, X., Chen, Y., (November 26,2016), New Differentially Expressed Genes and Differential DNA Methylation Underlying Refractory Epilepsy. Oncotarget. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=13642