Neuronal activity modifies the DNA methylation landscape in the adult brain

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping / methods
  • CpG Islands / genetics
  • CpG Islands / physiology
  • DNA Methylation / physiology*
  • Epigenomics / methods
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Genomics / methods
  • Hippocampus / cytology*
  • Hippocampus / physiology*
  • Mice
  • Molecular Sequence Data
  • Motor Activity / genetics
  • Neurons / physiology*
  • Physical Conditioning, Animal
  • Statistics as Topic

Associated data

  • GEO/GSE30493