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Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
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Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
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Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons

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Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Journal Article

Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons

2010
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Overview
In dividing cells, the epigenetic mechanism of DNA methylation is catalyzed by enzymes that maintain DNA methylation or act as a de novo methyltransferase. In this study, the authors find that DNA methyltransferases Dnmt1 and 3a have an active role in the maintenance of DNA methylation in postmitotic excitatory neurons. Results indicate that there is a redundancy between the two enzymes in neurons and that DNA methylation is essential for normal synaptic plasticity and memory formation. Dnmt1 and Dnmt3a are important DNA methyltransferases that are expressed in postmitotic neurons, but their function in the CNS is unclear. We generated conditional mutant mice that lack Dnmt1 , Dnmt3a or both exclusively in forebrain excitatory neurons and found that only double knockout (DKO) mice showed abnormal long-term plasticity in the hippocampal CA1 region together with deficits in learning and memory. Although we found no neuronal loss, hippocampal neurons in DKO mice were smaller than in the wild type; furthermore, DKO neurons showed deregulated expression of genes, including the class I MHC genes and Stat1 , that are known to contribute to synaptic plasticity. In addition, we observed a significant decrease in DNA methylation in DKO neurons. We conclude that Dnmt1 and Dnmt3a are required for synaptic plasticity, learning and memory through their overlapping roles in maintaining DNA methylation and modulating neuronal gene expression in adult CNS neurons.