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

Authors
 Won-Young Choi  ;  Ji-Hyun Hwang  ;  Ann-Na Cho  ;  Andrew J Lee  ;  Jungwoo Lee  ;  Inkyung Jung  ;  Seung-Woo Cho  ;  Lark Kyun Kim  ;  Young-Joon Kim 
Citation
 STEM CELL REVIEWS AND REPORTS, Vol.16(6) : 1316-1327, 2020-12 
Journal Title
 STEM CELL REVIEWS AND REPORTS 
ISSN
 2629-3269 
Issue Date
2020-12
Keywords
DNA methylation ; Induced pluripotent stem cell ; Intragenic CpG island ; NEUROD1 ; Neuronal progenitor cell
Abstract
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. Graphical Abstract The relationship between iCGI DNA methylation and expression of associated genes in neuronal developmental process. During iPSC to NPCdifferentiation, iCGI containing neural developmental genes show iCGI's DNA hypermethylation which is accompanied by gene activation and NEUROD1which is one of the core neuronal TFs interacts with hypermethylated iCGI regions.
Full Text
https://link.springer.com/article/10.1007/s12015-020-10041-6
DOI
10.1007/s12015-020-10041-6
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Lark Kyun(김락균) ORCID logo https://orcid.org/0000-0001-5983-4470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181467
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