Neuronal Activity Modifies the DNA Methylation Landscape in the Adult Brain

Overview

Journal Nat Neurosci

Date 2011 Aug 30

PMID 21874013

Citations 361

Authors

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

Affiliations

Soon will be listed here.

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 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.

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