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[摘要]：Overexpression of neuronal adaptor protein X11 beta has been shown to decrease the production of amyloid-beta, a toxic peptide deposited in Alzheimer's disease brains. Therefore, manipulation of the X11 beta level may represent a potential therapeutic strategy for Alzheimer's disease. As X11 beta expression can be regulated at the transcription level, we determined the genomic organization and the promoter of the human X11 beta gene, amyloid beta A4 precursor protein-binding family A member 2 (APBA2). By RNA ligase-mediated rapid amplification of cDNA ends, a single APBA2 transcription start site and the complete sequence of exon 1 were identified. The APBA2 promoter was located upstream of exon 1 and was more active in neurons. The core promoter contains several CpG dinucleotides, and was strongly suppressed by DNA methylation. In addition, mutagenesis analysis revealed a putative Pax5-binding site within the promoter. Together, APBA2 contains a potent neuronal promoter whose activity may be regulated by DNA methylation and Pax5. NeuroReport 23: 146-151 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. |
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