Neuronal activity modifies DNA methylation landscape in the adult brain

By Junjie U. Guo, Dengke K. Ma, Huan Mo, Madeleine P. Ball, M. Jang, M. Bonaguidi, Jacob A. Balazer, Hugh L. Eaves, Bin Xie, Eric C. Ford and 4 more. Nature Neuroscience, 2011

650 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/16a6f9b27a66d13c68109c7716884aa59f16cfba

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Citations in the corpus

DNA Methylation and Its Basic Function (2013, background): “However, in slowly dividing and nondividing cells such as the brain, gene body methylation is not associated with increased gene expression (Aran et al, 2011; Guo et al, 2011a, b; Xie et al, 2012).”
Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood (2012, background): “Epigenetic processes control several neurobiological and cognitive processes, including neurogenesis and brain development [2], neuronal activity [3], learning and memory [4], drug addiction [5], neurodegeneration [6], and circadian rhythm [7].”
Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options (2020, background): “In contrast to the genome, which is considered for the purposes of epilepsy to be largely (but not completely) fixed over time and across tissues, the epigenome can be very dynamic, varying even during short time periods (Guo et al., 2011) and across (and potentially within) organs.”
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, positive): “…adult neurogenesis, especially concerning maintenance and exit from quiescence in adult NSCs. Interestingly, DNA demethylation appears to be induced by neuronal activity in the DG, resulting in the proliferation of neural progenitors and growth of newborn DGCs (Guo et al., 2011a; Ma et al., 2009).”