KA exposure for 2 h to mouse hippocampal slices triggers DNAm of a 5' regulatory region of the gria2 gene. Increase in DNAm persists one week after removal of the drug, with concurrent suppression of gria2 mRNA expression levels. In a rat in vivo model of post kainic acid-induced epilepsy, we show similar hyperDNAm of the 5' region of gria2. Luciferase reporter assays support a regulatory role for DNAm of gria2 5' region. Inhibition of DNAm by RG108 blocked KA-induced hyperDNAm of gria2 5' region in HC slice cultures. The gene discussed is GRIA2; the disease is epilepsy.