| http://purl.uniprot.org/citations/22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22166205 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbrc.2011.11.123"xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Park Y.J."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Park M.H."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Seo J."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Rehli M."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Klug M."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Jo S.A."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Jo I."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/author | "Byun C.J."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/name | "Biochem Biophys Res Commun"xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/pages | "387-392"xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/title | "DNA methylation of the 5'-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells."xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://purl.uniprot.org/core/volume | "417"xsd:string |
| http://purl.uniprot.org/citations/22166205 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22166205 |
| http://purl.uniprot.org/citations/22166205 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22166205 |
| http://purl.uniprot.org/uniprot/#_P56818-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/#_Q8BQY4-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/#_Q69ZQ6-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/#_Q8C7R1-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/#_Q8C4F4-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/#_Q9CUU5-mappedCitation-22166205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22166205 |
| http://purl.uniprot.org/uniprot/P56818 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/22166205 |