DNA methylation of intragenic CpG islands are required for differentiation from iPSC to NPC

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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1316–1327
Number of pages12
JournalStem Cell Reviews and Reports
Volume16
Issue number6
DOIs
Publication statusPublished - Dec 2020
Externally publishedYes

Keywords

  • DNA methylation
  • Intragenic CpG island
  • Induced pluripotent stem cell
  • Neuronal progenitor cell
  • NEUROD1

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