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

Title
Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells
Authors
Jeong Y.Jun Y.Kim J.Park H.Choi K.-S.Zhang H.Park J.A.Kwon J.-Y.Kim Y.-M.Lee S.Kwon Y.-G.
Ewha Authors
이상혁
SCOPUS Author ID
이상혁scopus
Issue Date
2017
Journal Title
Gene
ISSN
0378-1119JCR Link
Citation
vol. 635, pp. 48 - 60
Keywords
DifferentiationDNA methylationEndothelial cellsGene discoveryMeDIP seqPromoter CpG islandsRNA seqUmbilical cord blood derived mononuclear cell
Publisher
Elsevier B.V.
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2017 The Authors
DOI
10.1016/j.gene.2017.09.006
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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