title: Linking DNA methyltransferases to epigenetic marks and nucleosome structure genome-wide in human tumor cells.
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.
authors.affiliation: Cancer Research Center, Georgia Health Sciences University, Augusta, GA 30912, USA.
authors.forename: Bilian
authors.initials: B
authors.lastname: Jin
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Rochelle L
authors.initials: RL
authors.lastname: Tiedemann
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xu
authors.forename: Suhas
authors.initials: S
authors.lastname: Sureshchandra
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Stephen
authors.initials: S
authors.lastname: Dalton
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Choi
authors.forename: Keith D
authors.initials: KD
authors.lastname: Robertson
mesh_terms: D018236:Carcinoma, Embryonal / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D057890:Epigenomics; D005807:Genes, Overlapping; D056426:Genetic Loci; D015894:Genome, Human; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D000097584:DNA Methyltransferase 3B
chemical_list: D002843:Chromatin; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D006657:Histones; D009707:Nucleosomes; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human