Neuronal activity modifies the DNA methylation landscape in the adult brain

被引：480

作者：

Guo, Junjie U. ^{[1
,2
]}

Ma, Dengke K. ^{[1
,3
]}

Mo, Huan ^{[4
]}

Ball, Madeleine P. ^{[5
]}

Jang, Mi-Hyeon ^{[1
,3
]}

Bonaguidi, Michael A. ^{[1
,3
]}

Balazer, Jacob A. ^{[6
]}

Eaves, Hugh L. ^{[4
]}

Xie, Bin ^{[7
]}

Ford, Eric ^{[8
]}

Zhang, Kun ^{[9
]}

Ming, Guo-li ^{[1
,2
,3
]}

Gao, Yuan ^{[1
,7
]}

Song, Hongjun ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Sch Med, Solomon Snyder Dept Neurosci, Baltimore, MD USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[4] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA USA

[5] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA

[6] Proofpoint Inc, Sunnyvale, CA USA

[7] Lieber Inst Brain Dev, Div Genom Epigenom & Bioinformat, Baltimore, MD USA

[8] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD USA

[9] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

来源：

NATURE NEUROSCIENCE | 2011年 / 14卷 / 10期

基金：

美国国家卫生研究院;

关键词：

REGULATES MEMORY FORMATION; EPIGENETIC REGULATION; GENE-REGULATION; DEMETHYLATION; CELLS; TRANSCRIPTION; PLASTICITY; GENOME; NEUROGENESIS; CANCER;

D O I：

10.1038/nn.2900

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1345 / U172

页数：9

共 50 条

[1] Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells [J].

Ball, Madeleine P. ;

Li, Jin Billy ;

Gao, Yuan ;

Lee, Je-Hyuk ;

LeProust, Emily M. ;

Park, In-Hyun ;

Xie, Bin ;

Daley, George Q. ;

Church, George M. .

NATURE BIOTECHNOLOGY, 2009, 27 (04) :361-368

[2] Decoding the Epigenetic Language of Neuronal Plasticity [J].

Borrelli, Emiliana ;

Nestler, Eric J. ;

Allis, C. David ;

Sassone-Corsi, Paolo .

NEURON, 2008, 60 (06) :961-974

[3] DNA methylation and memory formation [J].

Day, Jeremy J. ;

Sweatt, J. David .

NATURE NEUROSCIENCE, 2010, 13 (11) :1319-1323

[4] Circadian regulator CLOCK is a histone acetyltransferase [J].

Doi, Masao ;

Hirayama, Jun ;

Sassone-Corsi, Paolo .

CELL, 2006, 125 (03) :497-508

[5] Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation [J].

Dong, E. ;

Nelson, M. ;

Grayson, D. R. ;

Costa, E. ;

Guidotti, A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (36) :13614-13619

[6] MOM: maximum oligonucleotide mapping [J].

Eaves, Hugh L. ;

Gao, Yuan .

BIOINFORMATICS, 2009, 25 (07) :969-970

[7] Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice [J].

Elliott, Evan ;

Ezra-Nevo, Gili ;

Regev, Limor ;

Neufeld-Cohen, Adi ;

Chen, Alon .

NATURE NEUROSCIENCE, 2010, 13 (11) :1351-1353

[8] Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons [J].

Feng, Jian ;

Zhou, Yu ;

Campbell, Susan L. ;

Le, Thuc ;

Li, En ;

Sweatt, J. David ;

Silva, Alcino J. ;

Fan, Guoping .

NATURE NEUROSCIENCE, 2010, 13 (04) :423-U37

[9] Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain [J].

Ford, E. C. ;

Achanta, P. ;

Purger, D. ;

Armour, M. ;

Reyes, J. ;

Fong, J. ;

Kleinberg, L. ;

Redmond, K. ;

Wong, J. ;

Jang, M. H. ;

Jun, H. ;

Song, H-J. ;

Quinones-Hinojosa, A. .

RADIATION RESEARCH, 2011, 175 (06) :774-783

[10] HDAC2 negatively regulates memory formation and synaptic plasticity [J].

Guan, Ji-Song ;

Haggarty, Stephen J. ;

Giacometti, Emanuela ;

Dannenberg, Jan-Hermen ;

Joseph, Nadine ;

Gao, Jun ;

Nieland, Thomas J. F. ;

Zhou, Ying ;

Wang, Xinyu ;

Mazitschek, Ralph ;

Bradner, James E. ;

DePinho, Ronald A. ;

Jaenisch, Rudolf ;

Tsai, Li-Huei .

NATURE, 2009, 459 (7243) :55-U58

← 1 2 3 4 5 →