AI Article Synopsis
- - CpG islands (CGIs) are usually resistant to methylation in normal cells, but many cancers show CGI hypermethylation, suggesting issues with the cell's normal machinery.
- - During the study of somatic cell reprogramming, most CGIs remained hypomethylated, but certain imprinting control regions (ICRs) became methylated, which was tied to the silencing of key reprogramming factors late in the process.
- - The study found that the hypermethylation of specific ICRs was common in pediatric cancers, while adult cancers displayed widespread CGI hypermethylation, pointing to significant implications for understanding pediatric cancer development and using pluripotent stem cells (PSCs) in therapies
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524733 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2019.04.008 | DOI Listing |
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