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 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.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Junjie U
authors.initials: JU
authors.lastname: Guo
authors.forename: Dengke K
authors.initials: DK
authors.lastname: Ma
authors.forename: Huan
authors.initials: H
authors.lastname: Mo
authors.forename: Madeleine P
authors.initials: MP
authors.lastname: Ball
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bonaguidi
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Balazer
authors.forename: Hugh L
authors.initials: HL
authors.lastname: Eaves
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.forename: Eric
authors.initials: E
authors.lastname: Ford
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D018899:CpG Islands / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology*; D057890:Epigenomics / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D023281:Genomics / Q000379:methods; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D010805:Physical Conditioning, Animal; D013223:Statistics as Topic