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DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC.
Choi, Won-Young; Hwang, Ji-Hyun; Cho, Ann-Na; Lee, Andrew J; Lee, Jungwoo; Jung, Inkyung; Cho, Seung-Woo; Kim, Lark Kyun; Kim, Young-Joon.
Afiliación
  • Choi WY; Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul, 03722, Republic of Korea.
  • Hwang JH; Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul, 03722, Republic of Korea.
  • Cho AN; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
  • Lee AJ; Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
  • Lee J; Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul, 03722, Republic of Korea.
  • Jung I; Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
  • Cho SW; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
  • Kim LK; Severance Biomedical Science Institute and BK21 PLUS Project for Medical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06230, Republic of Korea. LKKIM@yuhs.ac.
  • Kim YJ; Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul, 03722, Republic of Korea. yjkim@yonsei.ac.kr.
Stem Cell Rev Rep ; 16(6): 1316-1327, 2020 12.
Article en En | MEDLINE | ID: mdl-32975781
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Islas de CpG / Metilación de ADN / Células Madre Pluripotentes Inducidas / Células-Madre Neurales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Rev Rep Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Islas de CpG / Metilación de ADN / Células Madre Pluripotentes Inducidas / Células-Madre Neurales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Rev Rep Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos