Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 조인호 | * |
dc.contributor.author | 서정원 | * |
dc.contributor.author | 박윤정 | * |
dc.date.accessioned | 2016-08-28T12:08:51Z | - |
dc.date.available | 2016-08-28T12:08:51Z | - |
dc.date.issued | 2012 | * |
dc.identifier.issn | 0006-291X | * |
dc.identifier.other | OAK-8400 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/222308 | - |
dc.description.abstract | BACE1, 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.language | English | * |
dc.title | DNA methylation of the 5′-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 417 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 387 | * |
dc.relation.lastpage | 392 | * |
dc.relation.journaltitle | Biochemical and Biophysical Research Communications | * |
dc.identifier.doi | 10.1016/j.bbrc.2011.11.123 | * |
dc.identifier.wosid | WOS:000299491600066 | * |
dc.identifier.scopusid | 2-s2.0-84855762409 | * |
dc.author.google | Byun C.J. | * |
dc.author.google | Seo J. | * |
dc.author.google | Jo S.A. | * |
dc.author.google | Park Y.J. | * |
dc.author.google | Klug M. | * |
dc.author.google | Rehli M. | * |
dc.author.google | Park M.-H. | * |
dc.author.google | Jo I. | * |
dc.contributor.scopusid | 조인호(26643129000;56663841900) | * |
dc.contributor.scopusid | 박윤정(55494373100) | * |
dc.date.modifydate | 20240215164841 | * |