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

Author(s)
Jin, Bilian; Ernst, Jason; Tiedemann, Rochelle L.; Xu, Hongyan; Sureshchandra, Suhas; Kellis, Manolis; Dalton, Stephen; Liu, Chen; Choi, Jeong-Hyeon; Robertson, Keith D.; ... Show more Show less
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Abstract
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.
Date issued
2012-11
URI
http://hdl.handle.net/1721.1/87008
Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Journal
Cell Reports
Publisher
Elsevier
Citation
Jin, Bilian, Jason Ernst, Rochelle L. Tiedemann, Hongyan Xu, Suhas Sureshchandra, Manolis Kellis, Stephen Dalton, Chen Liu, Jeong-Hyeon Choi, and Keith D. Robertson. “Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-Wide in Human Tumor Cells.” Cell Reports 2, no. 5 (November 2012): 1411–1424.
Version: Final published version
ISSN
22111247

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