Promoter characterization and genomic organization of the human X11β gene APBA2.
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.
Biochemistry Program, School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR.
Yan
Y
Hao
Ka-Ho
KH
Chai
Declan M
DM
McLoughlin
Ho Yin Edwin
HY
Chan
Kwok-Fai
KF
Lau
D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D019175:DNA Methylation; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
C491636:APBA2 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins