View : 217 Download: 0
DNA methylation of the 5′-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells
- DNA methylation of the 5′-untranslated region at +298 and +351 represses BACE1 expression in mouse BV-2 microglial cells
- Byun C.J.; Seo J.; Jo S.A.; Park Y.J.; Klug M.; Rehli M.; Park M.-H.; Jo I.
- Ewha Authors
- 조인호; 서정원; 박윤정
- SCOPUS Author ID
- 조인호; 박윤정
- Issue Date
- Journal Title
- Biochemical and Biophysical Research Communications
- Biochemical and Biophysical Research Communications vol. 417, no. 1, pp. 387 - 392
- SCI; SCIE; SCOPUS
- Document Type
Show the fulltext
- 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..
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.