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Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells

Authors
 Yoonjeong Jeong  ;  Yukyung Jun  ;  Jihye Kim  ;  Hyojin Park  ;  Kyu-Sung Choi  ;  Haiying Zhang  ;  Jeong Ae Park  ;  Ja-Young Kwon  ;  Young-Myeong Kim  ;  Sanghyuk Lee  ;  Young-Guen Kwon 
Citation
 Gene, Vol.635 : 48-60, 2017 
Journal Title
 Gene 
ISSN
 0378-1119 
Issue Date
2017
MeSH
Cell Differentiation/genetics* CpG Islands DNA Methylation/genetics* Endothelial Cells/cytology ; Endothelial Cells/metabolism* ; Epigenesis, Genetic ; Fetal Blood/cytology ; Fetal Blood/metabolism ; Gene Expression Regulation, Developmental ; Genome, Human ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism* ; Promoter Regions, Genetic ; RNA, Messenger/biosynthesis
Keywords
DNA methylation ; Differentiation ; Endothelial cells ; Gene discovery ; MeDIP seq ; Promoter CpG islands ; RNA seq ; Umbilical cord blood derived mononuclear cell
Abstract
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells. We identified 61 downregulated genes with hypermethylation, including CD74, VAV1, TLR8, and NCF4, as well as 21 upregulated genes with hypomethylation, including ECSCR, MCAM, PGF, and ARHGEF15. Interestingly, gene ontology analysis showed that downregulated genes with hypermethylation were enriched in immune-related functions, and upregulated genes with hypomethylation were enriched in the developmental process and angiogenesis, indicating the important roles of DNA methylation in regulating differentiation. We performed polymerase chain reaction analyses and bisulfite sequencing of representative genes (CD74, VAV1, ECSCR, and MCAM) to verify the negative correlation between DNA methylation and gene expression. Further, inhibition of DNA methyltransferase and demethylase activities using 5'-aza-dc and shRNAs, specific for TET1 and TET2 mRNAs, respectively, revealed that DNA methylation was the main regulator of the reversible expression of functionally important genes. Collectively, our findings implicate DNA methylation as a critical regulator of gene expression during umbilical cord blood derived mononuclear cells to endothelial cell differentiation.
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DOI
10.1016/j.gene.2017.09.006
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
권자영(Kwon, Ja Young) ORCID logo https://orcid.org/0000-0003-3009-6325
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161551
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