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Profiling of Chromatin States in a Human Cancer Cell Line

ABSTRACT: DNA methylation mediated by the combined action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B, is essential for mammalian development and is also a major contributor to transformation. To elucidate how DNA methylation is targeted, we map the genome-wide localization of all DNMTs and methylation, and examine relationships between these markers and histone modifications and nucleosome structure. Our findings reveal a strong link between DNA methylation/DNMTs and transcribed loci and that these marks exhibit both overlapping and unique localization patterns. Comparisons with the epigenome of embryonic stem cells demonstrate that DNMT binding is associated with transformation-associated changes in methylation. Taken together, this study sheds important new light on determinants of DNA methylation and how it may become disrupted in cancer cells. Examination of different marks in undifferentiated and differentiatial NCCIT cells

ORGANISM(S): Homo sapiens

SUBMITTER: Keith robertson

PROVIDER: E-GEOD-38937 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Linking DNA Methyltransferases (DNMTs) to Epigenetic Marks and Nucleosome Structure Genome-Wide in Human Tumor Cells

Project description:This SuperSeries is composed of the following subset Series: GSE38936: Expression data from human cancer cells GSE38937: Profiling of Chromatin States in a Human Cancer Cell Line Refer to individual Series

2012-10-19 | E-GEOD-38938 | biostudies-arrayexpress

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2014-10-20 | E-GEOD-54842 | biostudies-arrayexpress

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Project description:Global patterns of DNA methylation, mediated by the DNA methyltransferases (DNMTs), are disrupted in all cancers by mechanisms that remain largely unknown, hampering their development as therapeutic targets. Combinatorial acute depletion of all DNMTs in a pluripotent human tumor cell line, followed by epigenome and transcriptome analysis, revealed DNMT functions in unprecedented detail. DNMT3B occupancy regulates methylation during differentiation, while an unexpected interplay was discovered in which DNMT1 and DNMT3B antithetically regulate methylation and hydroxymethylation in gene bodies, a finding confirmed in other cell types. DNMT3B mediated nonCpG methylation, while DNMT3L influenced the activity of DNMT3B toward nonCpG versus CpG site methylation. Taken together, these data reveal new functional targets of each DNMT suggesting that isoform selective inhibition would be therapeutically advantageous. Overall, 27 samples were analyzed using the Infinium HumanMethylation450 BeadChip. 19 samples include NCCIT cells treated with various siRNAs targeting specific DNA methyltransferases. For the samples labeled biological replicate 1, NTC-1 serves as the control. Two additional biological replicates were analyzed for the siDNMT1, siDNMT3B, and si3B+3L condition; NTC-2 serves as the control for these samples. Six samples include HCT116 WT and various derivatives with alternative expression of DNMT1 and/or DNMT3B; WT serves as the control. Two samples include the undifferentiated (UD) and 7-day differentiated (DF) NCCIT cells; UD serves as the control.

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2022-02-24 | PXD003401 | Pride

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2011-02-01 | E-GEOD-26136 | biostudies-arrayexpress

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-01 | E-GEOD-36140 | biostudies-arrayexpress

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2020-02-28 | GSE139062 | GEO

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