Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine

被引：830

作者：

Song, Chun-Xiao ^{[1
,2
]}

Szulwach, Keith E. ^{[3
]}

Fu, Ye ^{[1
,2
]}

Dai, Qing ^{[4
]}

Yi, Chengqi ^{[1
,2
]}

Li, Xuekun ^{[3
]}

Li, Yujing ^{[3
]}

Chen, Chih-Hsin ^{[5
,6
]}

Zhang, Wen ^{[1
,2
]}

Jian, Xing ^{[1
,2
]}

Wang, Jing ^{[1
,2
]}

Zhang, Li ^{[5
,6
]}

Looney, Timothy J. ^{[5
,6
]}

Zhang, Baichen ^{[7
]}

Godley, Lucy A. ^{[8
]}

Hicks, Leslie M. ^{[7
]}

Lahn, Bruce T. ^{[5
,6
]}

Jin, Peng ^{[3
]}

He, Chuan ^{[1
,2
]}

机构：

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

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

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

[4] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[5] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[6] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA

[7] Donald Danforth Plant Sci Ctr, St Louis, MO USA

[8] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 01期

基金：

美国国家卫生研究院;

关键词：

DNA METHYLATION; CLICK CHEMISTRY; COPPER-FREE; 5-METHYLCYTOSINE; QUANTIFICATION; DEMETHYLATION; CONVERSION; CHROMATIN; PROTEINS; BRAIN;

D O I：

10.1038/nbt.1732

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

In contrast to 5-methylcytosine (5-mC), which has been studied extensively(1-3), little is known about 5-hydroxymethylcytosine (5-hmC), a recently identified epigenetic modification present in substantial amounts in certain mammalian cell types(4,5). Here we present a method for determining the genome-wide distribution of 5-hmC. We use the T4 bacteriophage beta-glucosyltransferase to transfer an engineered glucose moiety containing an azide group onto the hydroxyl group of 5-hmC. The azide group can be chemically modified with biotin for detection, affinity enrichment and sequencing of 5-hmC-containing DNA fragments in mammalian genomes. Using this method, we demonstrate that 5-hmC is present in human cell lines beyond those previously recognized(4). We also find a gene expression level-dependent enrichment of intragenic 5-hmC in mouse cerebellum and an age-dependent acquisition of this modification in specific gene bodies linked to neurodegenerative disorders.

引用

页码：68 / 72

页数：5

共 41 条

[41] Model-based Analysis of ChIP-Seq (MACS) [J].

Zhang, Yong ;

Liu, Tao ;

Meyer, Clifford A. ;

Eeckhoute, Jerome ;

Johnson, David S. ;

Bernstein, Bradley E. ;

Nussbaum, Chad ;

Myers, Richard M. ;

Brown, Myles ;

Li, Wei ;

Liu, X. Shirley .

GENOME BIOLOGY, 2008, 9 (09)

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