Ever notice how certain things can trigger unpleasant memories (like that sushi that gave you food poisoning)? Researchers have long wondered how these “contextual fear memories” get burned into our brains. A new study led by Farah Lubin at the University of Alabama at Birmingham has shown that histone methylation plays an important role in long-term memory formation.
The investigators studied histone methylation in the hippocampuses of adult rats that were placed briefly in an unfamiliar training chamber and given electric shocks. When the rats were returned to the chamber 24 h later, they froze in anticipation of a shock, indicating that they had formed long-term memories of the event. Analysis of hippocampal tissue after this contextual fear conditioning revealed some interesting epigenetic changes:
- H3K4 trimethylation, an active mark for transcription, was upregulated after conditioning. Mice deficient in an H3K4-specific histone methyltransferase showed defective long-term memory formation, as indicated by decreased freezing behavior.
- H3K9 dimethylation, a silencing-associated mark, also increased after fear conditioning.
- HDAC inhibition increased H3K4 trimethylation and decreased H3K9 dimethylation after contextual fear conditioning, indicating a link between histone acetylation and histone methylation.
- Fear conditioning increased H3K4 trimethylation and changed DNA methylation patterns in the promoters of Zif268 and bdnf, two genes critical for long-term memory formation.
Together, these results suggest that active regulation of histone methylation contributes to long-term memory formation. Don’t be afraid to check out all the details the Journal of Neuroscience, March 2010.