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| Status |
Public on Jun 12, 2020 |
| Title |
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (data set 1) |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Aberrant DNA hypermethylation of promoter CpG islands in the context of a hypomethylated genome is a hallmark of cancer. Thus far there is no human experimental model available to mechanistically investigate this phenomenon. Here we show that upon reprogramming of human embryonic stem cells to the naïve state, the acquisition of a globally hypomethylated genome is accompanied by hypermethylation of a subset of bivalent promoter CpG islands, resulting in a DNA methylome comparable to the human inner cell mass. We show that de novo methylation is carried out by DNMT3A and coordinated by the transcription factor network. We further show that the subset of bivalent sites that become hypermethyated are functionally distinct, with an enrichment in developmental genes, and demonstrate that this is mirrored in DNA hypermethylation patterns across cancer types, suggesting that common mechanisms may be responsible. We propose a wider utility of this experimental system to understand pre-malignant cancer-associated processes.
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| Overall design |
EPIC array data for n=2 Primed, early transition, late transition and naïve hESCs.
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| Contributor(s) |
Patani H, Rushton MD, Ficz G |
| Citation(s) |
32699299 |
| Submission date |
Mar 11, 2019 |
| Last update date |
Aug 03, 2020 |
| Contact name |
Hemalvi Patani |
| E-mail(s) |
hemalvi_179@hotmail.com
|
| Organization name |
Barts Cancer Institute
|
| Street address |
Charterhouse Square
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| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE128130 |
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation |
|
| Relations |
| BioProject |
PRJNA526514 |
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