@article{c2bc34ad0bc94be49265eced297959c9,
title = "Neuronal activity modifies the DNA methylation landscape in the adult brain",
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 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.",
author = "Guo, {Junjie U.} and Ma, {Dengke K.} and Huan Mo and Ball, {Madeleine P.} and Jang, {Mi Hyeon} and Bonaguidi, {Michael A.} and Balazer, {Jacob A.} and Eaves, {Hugh L.} and Bin Xie and Eric Ford and Kun Zhang and Ming, {Guo Li} and Yuan Gao and Hongjun Song",
note = "Funding Information: We thank G. Church, S. Baylin, D. Ginty and K. Christian for comments and suggestions; G. Sun for help with FACS; and W.Y. Kim (Johns Hopkins University) for breeding Gadd45b knockout mice. This work was supported by US National Institutes of Health (NIH; AG024984, NS047344), McKnight Scholar Award and NARSAD (Brain and Behavior Research Fund) to H.S.; by NIH (HD069184, NS048271), Johns Hopkins Brain Science Institute, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and NARSAD grants to G.-l.M.; and Lieber Institute start-up funds to Y.G. J.U.G. was a FARMS (Foundation for Advanced Research in Medical Sciences) fellow. M.H.J. was supported by a US National Institute of Mental Health K99 award (MH090115). M.A.B. was partially supported by a fellowship from Maryland Stem Cell Research Fund (MSCRF); M.P.B. was supported by grants from the NIH to G. Church.",
year = "2011",
month = oct,
doi = "10.1038/nn.2900",
language = "English (US)",
volume = "14",
pages = "1345--1351",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "10",
}