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Nat Neurosci. 2011 Aug 28;14(10):1345-51. doi: 10.1038/nn.2900.

Neuronal activity modifies the DNA methylation landscape in the adult brain.

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  • 1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

DNA methylation has been traditionally viewed as a highly stable epigenetic mark in postmitotic cells. However, postnatal brains appear to show stimulus-induced methylation changes, at least in a few identified CpG dinucleotides. How extensively the neuronal DNA methylome is regulated by neuronal activity is unknown. Using a next-generation sequencing-based method for genome-wide analysis at single-nucleotide resolution, we quantitatively compared the CpG methylation landscape of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation. About 1.4% of 219,991 CpGs measured showed rapid active demethylation or de novo methylation. Some modifications remained stable for at least 24 h. These activity-modified CpGs showed a broad genomic distribution with significant enrichment in low-CpG density regions, and were associated with brain-specific genes related to neuronal plasticity. Our study implicates modification of the neuronal DNA methylome as a previously underappreciated mechanism for activity-dependent epigenetic regulation in the adult nervous system.

© 2011 Nature America, Inc. All rights reserved.

PMID:
21874013
[PubMed - indexed for MEDLINE]
PMCID:
PMC3183401
Free PMC Article
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