section_path: Genetics/DNA methylation and demethylation
section_name: DNA methylation and demethylation
paragraph_text: DNA methylation and demethylation
  
  Rats exposed to an intense learning event may retain a life-long memory of the event, even after a single training session. The long-term memory of such an event appears to be initially stored in the hippocampus, but this storage is transient. Much of the long-term storage of the memory seems to take place in the anterior cingulate cortex. When such an exposure was experimentally applied, more than 5,000 differently methylated DNA regions appeared in the hippocampus neuronal genome of the rats at one and at 24 hours after training. These alterations in methylation pattern occurred at many genes that were downregulated, often due to the formation of new 5-methylcytosine sites in CpG rich regions of the genome. Furthermore, many other genes were upregulated, likely often due to hypomethylation. Hypomethylation often results from the removal of methyl groups from previously existing 5-methylcytosines in DNA. Demethylation is carried out by several proteins acting in concert, including the TET enzymes as well as enzymes of the DNA base excision repair pathway (see Epigenetics in learning and memory). The pattern of induced and repressed genes in brain neurons subsequent to an intense learning event likely provides the molecular basis for a long-term memory of the event.