Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells

被引：638

作者：

Pastor, William A. ^{[4
,5
,6
]}

Pape, Utz J. ^{[2
,4
,5
,7
]}

Huang, Yun ^{[6
]}

Henderson, Hope R. ^{[4
,5
,6
]}

Lister, Ryan ^{[8
]}

Ko, Myunggon ^{[6
]}

McLoughlin, Erin M. ^{[1
,3
]}

Brudno, Yevgeny ^{[9
]}

Mahapatra, Sahasransu ^{[6
]}

Kapranov, Philipp ^{[10
]}

Tahiliani, Mamta ^{[4
,5
]}

Daley, George Q. ^{[1
,3
]}

Liu, X. Shirley ^{[2
,7
]}

Ecker, Joseph R. ^{[8
]}

Milos, Patrice M. ^{[10
]}

Agarwal, Suneet ^{[1
,3
]}

Rao, Anjana ^{[4
,5
,6
]}

机构：

[1] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[3] Harvard Stem Cell Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[5] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

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

[7] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

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

[9] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[10] Helicos BioSci Corp, Cambridge, MA 02139 USA

来源：

NATURE | 2011年 / 473卷 / 7347期

基金：

美国国家科学基金会;

关键词：

DEVELOPMENTAL REGULATORS; MYELOID CANCERS; DNA METHYLATION; 5-METHYLCYTOSINE; HYDROXYLATION; TET1; QUANTIFICATION; SPECIFICATION; PLURIPOTENT; CONVERSION;

D O I：

10.1038/nature10102

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：

5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals(1-5). 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC)(1,2,4-7). 5hmC and TET proteins have been implicated in stem cell biology and cancer(1,4,5,8,9), but information on the genome-wide distribution of 5hmC is limited. Here we describe two novel and specific approaches to profile the genomic localization of 5hmC. The first approach, termed GLIB (glucosylation, periodate oxidation, biotinylation) uses a combination of enzymatic and chemical steps to isolate DNA fragments containing as few as a single 5hmC. The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation of CMS-containing DNA with a specific antiserum to CMS5. High-throughput sequencing of 5hmC-containing DNA from mouse embryonic stem (ES) cells showed strong enrichment within exons and near transcriptional start sites. 5hmC was especially enriched at the start sites of genes whose promoters bear dual histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 4 trimethylation (H3K4me3) marks. Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the 'poised' chromatin signature found at developmentally-regulated genes in ES cells.

引用

页码：394 / 397

页数：4

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