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
Mice RBRC00209