Epigenetic Mechanisms of Memory Consolidation

The requirement of gene transcription for memory consolidation has been established for several decades, but not until recently has it been recognized that epigenetic mechanisms play a role in the control of gene expression that leads to memory storage. Broadly speaking, these epigenetic mechanisms encompass changes in chromatin structure, such as posttranslational histone modifications and DNA methylation. Many studies have shown that histone acetylation is dynamically regulated after experience and that it acts as a permissive switch to allow gene transcription. These studies have established a dichotomy where permissive gene transcription results in memory enhancement and restrictive gene transcription in memory impairment. Other studies have focused on DNA methylation, specifically on the promoter region of genes, where it is associated with gene inactivation. Like histone acetylation, it has been shown that DNA methylation is regulated after experience, and can be dynamically regulated, although it is thought to be a more stable mark than histone acetylation. The relationship between levels of DNA methylation and memory impairment or enhancement is unclear and will require future study. Many other chromatin modifications play a role in experience-induced gene regulation, such as histone methylation and phosphorylation, as well as substitution by histone variants. Ultimately, these modifications in chromatin structure act in concert, in a potential combinatorial code, to regulate gene-specific transcription that results in memory consolidation.