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dc.contributor.author조인호-
dc.contributor.author서정원-
dc.contributor.author박윤정-
dc.date.accessioned2016-08-28T12:08:51Z-
dc.date.available2016-08-28T12:08:51Z-
dc.date.issued2012-
dc.identifier.issn0006-291X-
dc.identifier.otherOAK-8400-
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/222308-
dc.description.abstractBACE1, which cleaves the amyloid precursor protein, is the rate-limiting enzyme for β-amyloid peptide production, leading to the pathogenesis of Alzheimer's disease (AD). A high plasma level of homocysteine, acting as a potent methyltransferase inhibitor, is assumed to be a risk factor for AD onset. Using the demethylating drug 5-aza-2'-deoxycytidine (5-Aza), we tested whether and how BACE1 expression is regulated in mouse BV-2 microglial cells. 5-Aza increased both BACE1 mRNA and protein levels in a dose-dependent manner. Bisulfite-sequencing analysis revealed that two CpG sites at positions +298 and +351 in the 5'-untranslated region (5'-UTR) of the BACE1 gene were specifically demethylated in BV-2 cells treated with 5-Aza. In silico analysis showed that the +351 site is the STAT3/CTCF-binding site; the function of the +298 site has not been identified. To assess whether these two CpG sites play an important role in 5-Aza-induced transcriptional activation of BACE1, we constructed a BACE1 gene promoter including the 5'-UTR (-1136 to +500) fused to a CpG-free luciferase gene (pCpGL-BACE1) and its mutant pCpGL-BACE1-AA, which has substituted CG dinucleotides at the two CpG sites of pCpGL-BACE1 to AA. Promoter analysis showed a significant decrease (~30%) in the activity of pCpGL-BACE1-AA compared with that of pCpGL-BACE1. Furthermore, in vitro methylation of these two reporter constructs showed a complete silencing of their promoter activities. Our data demonstrate that BACE1 gene expression is regulated by DNA methylation of at least two CpG sites at positions +298 and +351 in the 5'-UTR in BV-2 microglial cells. © 2011 Elsevier Inc..-
dc.languageEnglish-
dc.titleDNA methylation of the 5′-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells-
dc.typeArticle-
dc.relation.issue1-
dc.relation.volume417-
dc.relation.indexSCI-
dc.relation.indexSCIE-
dc.relation.indexSCOPUS-
dc.relation.startpage387-
dc.relation.lastpage392-
dc.relation.journaltitleBiochemical and Biophysical Research Communications-
dc.identifier.doi10.1016/j.bbrc.2011.11.123-
dc.identifier.wosidWOS:000299491600066-
dc.identifier.scopusid2-s2.0-84855762409-
dc.author.googleByun C.J.-
dc.author.googleSeo J.-
dc.author.googleJo S.A.-
dc.author.googlePark Y.J.-
dc.author.googleKlug M.-
dc.author.googleRehli M.-
dc.author.googlePark M.-H.-
dc.author.googleJo I.-
dc.contributor.scopusid조인호(26643129000)-
dc.contributor.scopusid박윤정(55494373100)-
dc.date.modifydate20210416081004-
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의과대학 > 의학과 > Journal papers
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