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| Status |
Public on Oct 20, 2014 |
| Title |
Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome [MBD-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| 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 depltion 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.
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| Overall design |
NCCIT cells were transfected with siRNAs against DNMT3B and a no-target control. Genomic DNA was extracted, and subsequently applied to affinity MBD-bound magnetic beads (Ribomed) to enrich methylated DNA sequences.
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| 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 |
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| Submission date |
Feb 10, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Keith D Robertson |
| E-mail(s) |
robertson.keith@mayo.edu
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| Phone |
507-266-4886
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| Organization name |
Mayo Clinic
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| Department |
Molecular Pharmacology & Experimental Therapeutics
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| Lab |
Epigenetic Etiology of Human Disease Laboratory
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| Street address |
200 First Street SW, Stabile 12-70
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE54843 |
Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome |
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| Relations |
| BioProject |
PRJNA237802 |
| SRA |
SRP037548 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54842_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of BED, BIGWIG, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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