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Promoter characterization and genomic organization of the human X11β gene APBA2.Hao, Yan; Chai, Ka-Ho; McLoughlin, Declan M; Chan, Ho Yin Edwin; Lau, Kwok-Fai; Biochemistry Program, School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR. (2012-02-15)Overexpression of neuronal adaptor protein X11β has been shown to decrease the production of amyloid-β, a toxic peptide deposited in Alzheimer's disease brains. Therefore, manipulation of the X11β level may represent a potential therapeutic strategy for Alzheimer's disease. As X11β expression can be regulated at the transcription level, we determined the genomic organization and the promoter of the human X11β gene, amyloid β 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.