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Nat Neurosci. 2016 Jan;19(1):102-10. doi: 10.1038/nn.4194. Epub 2015 Dec 14.

DNA methylation changes in plasticity genes accompany the formation and maintenance of memory.

Author information

Research Group for Epigenetic Mechanisms in Dementia, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Research Group for Computational Systems Biology, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
German Center of Neurodegenerative Diseases (DZNE), Munich, Germany.
Biomedical Center, Ludwig Maximilians University Munich, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.


The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.

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