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

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dc.contributor.author권자영-
dc.date.accessioned2018-07-20T11:57:35Z-
dc.date.available2018-07-20T11:57:35Z-
dc.date.issued2017-
dc.identifier.issn0378-1119-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/161551-
dc.description.abstractDifferentiation 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.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherElsevier/North-Holland-
dc.relation.isPartOfGENE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHCell Differentiation/genetics* CpG Islands DNA Methylation/genetics* Endothelial Cells/cytology-
dc.subject.MESHEndothelial Cells/metabolism*-
dc.subject.MESHEpigenesis, Genetic-
dc.subject.MESHFetal Blood/cytology-
dc.subject.MESHFetal Blood/metabolism-
dc.subject.MESHGene Expression Regulation, Developmental-
dc.subject.MESHGenome, Human-
dc.subject.MESHHumans-
dc.subject.MESHLeukocytes, Mononuclear/cytology-
dc.subject.MESHLeukocytes, Mononuclear/metabolism*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHRNA, Messenger/biosynthesis-
dc.titleIntegrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Obstetrics & Gynecology-
dc.contributor.googleauthorYoonjeong Jeong-
dc.contributor.googleauthorYukyung Jun-
dc.contributor.googleauthorJihye Kim-
dc.contributor.googleauthorHyojin Park-
dc.contributor.googleauthorKyu-Sung Choi-
dc.contributor.googleauthorHaiying Zhang-
dc.contributor.googleauthorJeong Ae Park-
dc.contributor.googleauthorJa-Young Kwon-
dc.contributor.googleauthorYoung-Myeong Kim-
dc.contributor.googleauthorSanghyuk Lee-
dc.contributor.googleauthorYoung-Guen Kwon-
dc.identifier.doi10.1016/j.gene.2017.09.006-
dc.contributor.localIdA00246-
dc.relation.journalcodeJ00921-
dc.identifier.eissn1879-0038-
dc.identifier.pmid28887159-
dc.subject.keywordDNA methylation-
dc.subject.keywordDifferentiation-
dc.subject.keywordEndothelial cells-
dc.subject.keywordGene discovery-
dc.subject.keywordMeDIP seq-
dc.subject.keywordPromoter CpG islands-
dc.subject.keywordRNA seq-
dc.subject.keywordUmbilical cord blood derived mononuclear cell-
dc.contributor.alternativeNameKwon, Ja Young-
dc.contributor.affiliatedAuthorKwon, Ja Young-
dc.citation.volume635-
dc.citation.startPage48-
dc.citation.endPage60-
dc.identifier.bibliographicCitationGENE, Vol.635 : 48-60, 2017-
dc.identifier.rimsid61580-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers

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