Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-wide in Human Tumor Cells

被引：87

作者：

Jin, Bilian ^{[1
]}

Ernst, Jason ^{[3
,4
]}

Tiedemann, Rochelle L. ^{[1
]}

Xu, Hongyan ^{[1
,2
]}

Sureshchandra, Suhas ^{[1
,2
]}

Kellis, Manolis ^{[3
,4
]}

Dalton, Stephen ^{[5
]}

Liu, Chen ^{[6
]}

Choi, Jeong-Hyeon ^{[1
,2
]}

Robertson, Keith D. ^{[1
]}

机构：

[1] Georgia Hlth Sci Univ, Canc Res Ctr, Augusta, GA 30912 USA

[2] Georgia Hlth Sci Univ, Dept Biostat, Augusta, GA 30912 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[5] Univ Georgia, Paul D Coverdell Ctr Biomed & Hlth Sci, Athens, GA 30602 USA

[6] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

来源：

CELL REPORTS | 2012年 / 2卷 / 05期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; DNMT3B; HYPERMETHYLATION; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; ORGANIZATION; REPLICATION; PATTERNS;

D O I：

10.1016/j.celrep.2012.10.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

DNA methylation, mediated by the combined action of three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), is essential for mammalian development and is a major contributor to cellular transformation. To elucidate how DNA methylation is targeted, we mapped the genome-wide localization of all DNMTs and methylation, and examined the relationships among these markers, histone modifications, and nucleosome structure in a pluripotent human tumor cell line in its undifferentiated and differentiated states. Our findings reveal a strong link between DNMTs and transcribed loci, and that DNA methylation is not a simple sum of DNMT localization patterns. A comparison of the epigenomes of normal and cancerous stem cells, and pluripotent and differentiated states shows that the presence of at least two DNMTs is strongly associated with loci targeted for DNA hypermethylation. Taken together, these results shed important light on the determinants of DNA methylation and how it may become disrupted in cancer cells.

引用

页码：1411 / 1424

页数：14

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