Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-wide in Human Tumor Cells
Name
Kellis_Linking DNA.pdf
Size
2.91 MB
Format
Adobe PDF
Checksum (MD5)
d445da25ee1cce10a55e17d2c7090320
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.
Date Issued
November 2012
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
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.celrep.2012.10.017
