Neuronal activity modifies the DNA methylation landscape in the adult brain

Junjie U. Guo, Dengke K. Ma, Huan Mo, Madeleine P. Ball, Mi Hyeon Jang, Michael A. Bonaguidi, Jacob A. Balazer, Hugh L. Eaves, Bin Xie, Eric Ford, Kun Zhang, Guo Li Ming, Yuan Gao, Hongjun Song

Research output: Contribution to journalArticlepeer-review


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 sequencingĝ€ "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.

Original languageEnglish (US)
Pages (from-to)1345-1351
Number of pages7
JournalNature neuroscience
Issue number10
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Neuroscience(all)


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