Neuronal activity modifies the DNA methylation landscape in the adult brain

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

doi:10.1038/nn.2900

Neuronal activity modifies the DNA methylation landscape in the adult brain

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

Research output: Contribution to journal › Article › peer-review

442 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1345-1351
Number of pages	7
Journal	Nature neuroscience
Volume	14
Issue number	10
DOIs	https://doi.org/10.1038/nn.2900
State	Published - Oct 2011
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1038/nn.2900

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@article{e6f3e24e9f034cacafc3c499cadaad9e,

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",

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number = "10",

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T1 - Neuronal activity modifies the DNA methylation landscape in the adult brain

AU - Guo, Junjie U.

AU - Ma, Dengke K.

AU - Mo, Huan

AU - Ball, Madeleine P.

AU - Jang, Mi Hyeon

AU - Bonaguidi, Michael A.

AU - Balazer, Jacob A.

AU - Eaves, Hugh L.

AU - Xie, Bin

AU - Ford, Eric

AU - Zhang, Kun

AU - Ming, Guo Li

AU - Gao, Yuan

AU - Song, Hongjun

N1 - 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.

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

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JO - Nature neuroscience

JF - Nature neuroscience

IS - 10

ER -

Neuronal activity modifies the DNA methylation landscape in the adult brain

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