TY - JOUR
T1 - Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-wide in Human Tumor Cells
AU - Jin, Bilian
AU - Ernst, Jason
AU - Tiedemann, Rochelle L.
AU - Xu, Hongyan
AU - Sureshchandra, Suhas
AU - Kellis, Manolis
AU - Dalton, Stephen
AU - Liu, Chen
AU - Choi, Jeong Hyeon
AU - Robertson, Keith D.
N1 - Funding Information:
We thank Kip Bodi and the Tufts University Genomics Core Facility for assistance with Illumina sequencing, and Keji Zhao (National Heart, Lung, and Blood Institute) for providing advice on nucleosome positioning experiments. This work was supported by the National Institutes of Health (grants R01CA114229, R01CA116028, and R01AA019976 to K.D.R.; RC1HG005334 to M.K.; and P01GM08535403 to S.D. and K.D.R. [pilot fund]) and the National Science Foundation (postdoctoral fellowship 0905968 to J.E.). K.D.R. is a Georgia Cancer Coalition Distinguished Cancer Scholar.
PY - 2012/11/29
Y1 - 2012/11/29
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2012.10.017
DO - 10.1016/j.celrep.2012.10.017
M3 - Article
C2 - 23177624
AN - SCOPUS:84870412337
SN - 2211-1247
VL - 2
SP - 1411
EP - 1424
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -
