Global Epigenomic Reconfiguration During Mammalian Brain Development

被引：1366

作者：

Lister, Ryan ^{[1
,2
,3
]}

Mukamel, Eran A. ^{[4
]}

Nery, Joseph R. ^{[1
]}

Urich, Mark ^{[1
]}

Puddifoot, Clare A. ^{[4
]}

Johnson, Nicholas D. ^{[4
]}

Lucero, Jacinta ^{[4
]}

Huang, Yun ^{[5
,6
]}

Dwork, Andrew J. ^{[7
,8
,9
]}

Schultz, Matthew D. ^{[1
,10
]}

Yu, Miao ^{[11
,12
]}

Tonti-Filippini, Julian ^{[2
,3
]}

Heyn, Holger ^{[13
]}

Hu, Shijun ^{[14
]}

Wu, Joseph C. ^{[14
]}

Rao, Anjana ^{[5
,6
]}

Esteller, Manel ^{[13
,15
]}

He, Chuan ^{[11
,12
]}

Haghighi, Fatemeh G. ^{[7
,8
]}

Sejnowski, Terrence J. ^{[4
,16
,17
]}

Behrens, M. Margarita ^{[4
]}

Ecker, Joseph R. ^{[1
,17
]}

机构：

[1] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA

[2] Univ Western Australia, Sch Chem & Biochem, Plant Energy Biol Australian Res Council Ctr Exce, Perth, WA 6009, Australia

[3] Univ Western Australia, Sch Chem & Biochem, Computat Syst Biol Western Australia CoE, Perth, WA 6009, Australia

[4] Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA

[5] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA

[6] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA

[7] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[8] New York State Psychiat Inst & Hosp, New York, NY 10032 USA

[9] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[10] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA

[11] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[12] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[13] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Canc Epigenet Grp, Barcelona 08907, Spain

[14] Stanford Univ, Sch Med, Dept Med, Div Cardiol, Stanford, CA 94305 USA

[15] ICREA, Barcelona, Catalonia, Spain

[16] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92037 USA

[17] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

来源：

SCIENCE | 2013年 / 341卷 / 6146期

基金：

澳大利亚研究理事会;

关键词：

HUMAN PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; EMBRYONIC STEM-CELLS; DNA METHYLATION; ACCESSIBLE CHROMATIN; DEOXYRIBONUCLEIC-ACID; TRANSCRIPTION FACTOR; SYNAPTIC PLASTICITY; MEMORY FORMATION; NERVOUS-SYSTEM;

D O I：

10.1126/science.1237905

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

引用

页码：629 / +

页数：13

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