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| Status |
Public on Jun 18, 2019 |
| Title |
De novo DNA methylation at imprinted loci during reprogramming into naïve and primed pluripotency |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during the somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, were often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs.
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| Overall design |
Analyzing DNA methylation profiles and transcriptional profiles by Methylseq and RNA-seq in ESCs, EpiSCs, iPSCs and iEpiSCs with F1 genetic background between 129/SvJ and MSM/Ms and various tissues obtained from E14.5 embryos.
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| Contributor(s) |
Yagi M, Kabata M, Yamamoto T, Yamada Y |
| Citation(s) |
31056481, 32581223 |
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| Submission date |
Feb 27, 2018 |
| Last update date |
Jun 29, 2020 |
| Contact name |
Yasuhiro Yamada |
| E-mail(s) |
[email protected]
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| Organization name |
University of Tokyo
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| Department |
Department of Molecular Pathology
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| Street address |
7-3-1 Hongo, Bunkyo-ku
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| City |
Tokyo |
| ZIP/Postal code |
113-0033 |
| Country |
Japan |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA436116 |
| SRA |
SRP133566 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE111173_ProcessedDataMatrixRPKMfin.STAR.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE111173_RAW.tar |
710.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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