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Series GSE54840 Query DataSets for GSE54840
Status Public on Oct 20, 2014
Title Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome [methylation]
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary 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 design 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.
Contributor(s) Tiedemann RL, Putiri EL, Lee JH, Hlady RA, Kashiwagi K, Ordog T, Zhang Z, Liu C, Choi JH, Robertson KD
Citation(s) 25453758, 25792550
Submission date Feb 10, 2014
Last update date Mar 22, 2019
Contact name Keith D Robertson
Phone 507-266-4886
Organization name Mayo Clinic
Department Molecular Pharmacology & Experimental Therapeutics
Lab Epigenetic Etiology of Human Disease Laboratory
Street address 200 First Street SW, Stabile 12-70
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (27)
GSM1324989 NCCIT_siRNA_NTC (biological replicate 1)
GSM1324990 NCCIT_siRNA_DNMT1 (biological replicate 1)
GSM1324991 NCCIT_siRNA_D1+3A
This SubSeries is part of SuperSeries:
GSE54843 Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome
BioProject PRJNA237803

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE54840_RAW.tar 183.1 Mb (http)(custom) TAR
GSE54840_methylated_unmethylated_signals.txt.gz 65.2 Mb (ftp)(http) TXT
Processed data included within Sample table

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