Friday, March 16, 2007

Epigenetics in memory   posted by amnestic @ 3/16/2007 08:13:00 AM

There's a new article by Miller and Sweatt in Neuron claiming that DNA methylation is a step in memory formation. They show methylation and demethylation of particular genes (reelin and PP1) following fear conditioning, and they show that inhibition of DNA methyl transferases (the name says it all) during the memory consolidation can disrupt memory. I hope now that they've started naming genes at which the methylation matters they'll study something more specific. The idea of inhibiting all DNA methylation in a cell for any length of time seems too blunt an instrument. The cells responsible for that memory could've just keeled over or radicaly changed because some cell cycle regulator got turned up too high for instance. They do show that animals can form a new, strong memory a couple days after administration of the drug, but in some cases, animals with a hippocampal lesion can perform these tasks. The nervous system can achieve learning (especially learning as important as conditioned fear) through many means, so seemingly normal behavior after an insult isn't that strong a control.

The scope of the processes disrupted by a DNMT inhibitor is indicated by this sentence from Miller and Sweatt:
Many developmentally important processes utilize this "prima donna" of epigenetics (Scarano et al., 2005 and Santos et al., 2005), including gene imprinting, cell differentiation, X chromosome inactivation, and long-term transcriptional regulation (Bestor et al., 1988 and Okano et al., 1998).

Sorry to be such a naysayer. It is an interesting hypothesis. It is likely the case that DNA methylation is regulated during memory formation. If we just think that memory will require transcriptional regulation then probably some DNA modifications will have to be done and undone. Cis-regulatory sequences that control a gene's level of activation can act through recruitment of histone acetyl transferases and other chromatin modifiers, so a precedent exists. But I don't think there is any special connection between epigenetics and memory. Memory requires cells to be cells and work properly, so it will require transcriptional regulation and DNA/chromatin modification. For any further connection, I think we have to start naming names.

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