5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging

被引：622

作者：

Szulwach, Keith E. ^{[1
]}

Li, Xuekun ^{[1
]}

Li, Yujing ^{[1
]}

Song, Chun-Xiao ^{[2
,3
]}

Wu, Hao ^{[4
]}

Dai, Qing ^{[2
,3
]}

Irier, Hasan ^{[1
]}

Upadhyay, Anup K. ^{[5
]}

Gearing, Marla ^{[6
]}

Levey, Allan I. ^{[6
]}

Vasanthakumar, Aparna ^{[7
]}

Godley, Lucy A. ^{[7
]}

Chang, Qiang ^{[8
]}

Cheng, Xiaodong ^{[5
]}

He, Chuan ^{[2
,3
]}

Jin, Peng ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA

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

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

[4] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

[5] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[6] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA

[7] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA

[8] Univ Wisconsin, Waisman Ctr, Dept Genet & Neurol, Madison, WI 53705 USA

来源：

NATURE NEUROSCIENCE | 2011年 / 14卷 / 12期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; CPG-BINDING PROTEIN-2; DNA METHYLATION; L1; RETROTRANSPOSITION; RETT-SYNDROME; ADULT NEUROGENESIS; BDNF TRANSCRIPTION; MEMORY FORMATION; MECP2; 5-HYDROXYMETHYLCYTOSINE;

D O I：

10.1038/nn.2959

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for similar to 40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC-regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5-hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl-CpG-binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC-mediated epigenetic modification is critical in neurodevelopment and diseases.

引用

页码：1607 / U150

页数：12

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