Neuronal activity modifies the DNA methylation landscape in the adult brain

作者：Guo Junjie U; Ma Dengke K; Mo Huan; Ball Madeleine P; Jang Mi Hyeon; Bonaguidi Michael A; Balazer Jacob A; Eaves Hugh L; Xie Bin; Ford Eric; Zhang Kun; Ming Guo li; Gao Yuan; Song Hongjun^*

来源：Nature Neuroscience, 2011, 14(10): 1345-U172.

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.

• 出版日期2011-10