DNA methylation of the 5 '-untranslated region at+298 and+351 represses BACE1 expression in mouse BV-2 microglial cells
DC Field | Value | Language |
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dc.contributor.author | Byun, Catherine Jeonghae | - |
dc.contributor.author | Seo, Jungwon | - |
dc.contributor.author | Jo, Sangmee Ahn | - |
dc.contributor.author | Park, Yoon Jung | - |
dc.contributor.author | Klug, Maja | - |
dc.contributor.author | Rehli, Michael | - |
dc.contributor.author | Park, Moon-Ho | - |
dc.contributor.author | Jo, Inho | - |
dc.date.accessioned | 2021-09-06T23:11:03Z | - |
dc.date.available | 2021-09-06T23:11:03Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2012-01-06 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/109092 | - |
dc.description.abstract | BACE1, which cleaves the amyloid precursor protein, is the rate-limiting enzyme for beta-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 (similar to 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. (C) 2011 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.subject | AMYLOID PRECURSOR PROTEIN | - |
dc.subject | PLASMA HOMOCYSTEINE | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | BETA-SECRETASE | - |
dc.subject | S-ADENOSYLHOMOCYSTEINE | - |
dc.subject | STEM-CELLS | - |
dc.subject | INCREASES | - |
dc.subject | GENE | - |
dc.subject | HYPOMETHYLATION | - |
dc.subject | PRESENILIN-1 | - |
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.contributor.affiliatedAuthor | Park, Moon-Ho | - |
dc.identifier.doi | 10.1016/j.bbrc.2011.11.123 | - |
dc.identifier.scopusid | 2-s2.0-84855762409 | - |
dc.identifier.wosid | 000299491600066 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.417, no.1, pp.387 - 392 | - |
dc.relation.isPartOf | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 417 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 387 | - |
dc.citation.endPage | 392 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.subject.keywordPlus | AMYLOID PRECURSOR PROTEIN | - |
dc.subject.keywordPlus | PLASMA HOMOCYSTEINE | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | BETA-SECRETASE | - |
dc.subject.keywordPlus | S-ADENOSYLHOMOCYSTEINE | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | INCREASES | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | HYPOMETHYLATION | - |
dc.subject.keywordPlus | PRESENILIN-1 | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | 5 &apos | - |
dc.subject.keywordAuthor | -Untranslated region | - |
dc.subject.keywordAuthor | BACE1 | - |
dc.subject.keywordAuthor | DNA methylation | - |
dc.subject.keywordAuthor | Microglial cells | - |
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