| RRC ID |
57684
|
| Author |
Yagi M, Kabata M, Ukai T, Ohta S, Tanaka A, Shimada Y, Sugimoto M, Araki K, Okita K, Woltjen K, Hochedlinger K, Yamamoto T, Yamada Y.
|
| Title |
De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency.
|
| Journal |
Stem Cell Reports
|
| Abstract |
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 somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, was 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.
|
| Volume |
12(5)
|
| Pages |
1113-1128
|
| Published |
2019-5-14
|
| DOI |
10.1016/j.stemcr.2019.04.008
|
| PII |
S2213-6711(19)30130-4
|
| PMID |
31056481
|
| PMC |
PMC6524733
|
| MeSH |
Adult
Animals
Cells, Cultured
Cellular Reprogramming / genetics*
CpG Islands / genetics
DNA Methylation / genetics*
Epigenesis, Genetic / genetics
Female
Genomic Imprinting / genetics*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism
Male
Mice, 129 Strain
Mice, Inbred ICR
Pluripotent Stem Cells / cytology
Pluripotent Stem Cells / metabolism*
|
| IF |
6.032
|
| Times Cited |
1
|
| Resource |
| Mice |
RBRC00209 |
