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.
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Neuronal activity modifies the DNA methylation landscape in the adult brain. / Guo, Junjie U.; Ma, Dengke K.; Mo, Huan; Ball, Madeleine P.; Jang, Mi-Hyeon D; Bonaguidi, Michael A.; Balazer, Jacob A.; Eaves, Hugh L.; Xie, Bin; Ford, Eric; Zhang, Kun; Ming, Guo Li; Gao, Yuan; Song, Hongjun.In: Nature Neuroscience, Vol. 14, No. 10, 10.2011, p. 1345-1351.
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