The connection between memory and epigenetics has been has been a hot topic over the last couple of years. A recent article in Nature Neuroscience adds a new wrinkle to the subject by showing that DNA methylation helps to save memories, in addition to creating them. Sort of like using the “Keep Until I Delete” function on your TiVo.
As we’ve previously highlighted, similar efforts have already outlined roles for non-coding RNAs, histone methylation, and H4K12 acetylation in memory formation, but less is known about memory maintenance. (So, if you’ve forgotten about these research highlights, one of these mechanisms is probably to blame.)
Savvy scientists from the University of Alabama at Birmingham studied the role that cytosine methylation plays in long-term memory development in trained rats. Their work focused on CpG island methylation in Egr 1, Reln and CaN – genes associated with memory formation.
- The team studied temporal changes in CpG island methylation using methylated DNA immunoprecipitation (MeDIP) and saw differential patterning in the onset and persistence of CaN hypermethylation after training.
- Specific changes in DNA methylation were then mapped with bisulfite sequencing, finding CaN hypermethylation only in the conditioned rats.
- They found that the NMDA antagonist drugs MK-801 and AP5 were able to block both memory formation and hypermethylation, confirming the link between the two.
- DNMT inhibitors 5-aza, zeb and RG108 were used to show that, while treatment 1 day after conditioning (before long-term memory formation) showed no effect, infusion at day 30 showed reduced memory formation and hypermethylation, indicating that DNA methylation preserves remote memories.
The hard work put in by UAB’s researchers moves us that much closer to understanding how memory works… but we’re still holding out for something that will help us dominate our friends in Trivial Pursuit. Refresh your memory at Nature Neuroscience, May 2010.