Studies of Histone H3 Methylation during the Formation of Long-Term Memory

Post-translational modification of histones plays in important role in chromatin remodeling and is involved in regulating gene expression during the formation of long-term memory. While histone acetylation and phosphorylation have been studied intensely for several years, studies of the role of methylation in learning have barely started. Histone methylation is interesting because it can both activate and inhibit gene expression. In a model of learning a conditioned defensive food aversion reflex in the mollusk Helix , we analyzed histone H3 trimethylation at lysine 4 (H3K4) and histone H3 dimethylation at lysine 9 (H3K9), which are associated with gene induction and repression respectively. These experiments showed that on consolidation of long-term memory, the Helix CNS shows a significant increase in histone H3 methylation at both lysine 4 and lysine 9. These data provide evidence for the involvement of histone methylation in the epigenetic mechanisms of formation of long-term memory in the mollusk Helix both at the levels of both activation and repression of transcription. In addition, induction of histone H3 methylation at lysine 9 was found to reflect the influences of inhibitory processes, which play an important role in CNS functioning.