DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC

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The effects of gene body DNA methylation on gene regulation still remains highly controversial. In this study, we generated whole genome bisulfite sequencing (WGBS) data with high sequencing depth in induced pluripotent stem cell (iPSC) and neuronal progentior cell (NPC), and investigated the relationship between DNA methylation changes in CpG islands (CGIs) and corresponding gene expression during NPC differentiation. Interestingly, differentially methylated CGIs were more abundant in intragenic regions compared to promoters and these methylated intragenic CGIs (iCGIs) were associated with neuronal development-related genes. When we compared gene expression level of methylated and unmethylated CGIs in intragenic regions, DNA methylation of iCGI was positively correlated with gene expression in contrast with promoter CGIs (pCGIs). To gain insight into regulatory mechanism mediated by iCGI DNA methylation, we executed motif searching in hypermethylated iCGIs and found NEUROD1 as a hypermethylated iCGI binding transcription factor. This study highlights give rise to possibility of activating role of hypermethylation in iCGIs and involvement of neuronal development related TFs.
Publisher
SPRINGER
Issue Date
2020-12
Language
English
Article Type
Article
Citation

STEM CELL REVIEWS AND REPORTS, v.16, no.6, pp.1316 - 1327

ISSN
2629-3269
DOI
10.1007/s12015-020-10041-6
URI
http://hdl.handle.net/10203/280071
Appears in Collection
BS-Journal Papers(저널논문)
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