Study of the Alzheimer's A4 precursor gene promoter region by genomic sequencing using Taq polymerase.
The beta-amyloid protein has been identified as the prominent component of the fibrillary aggregates of the neuritic plaques found in Alzheimer's disease (AD). In this paper, the DNA methylation pattern of the promoter region of the Alzheimer's disease amyloid precursor gene (PAD) was assessed using the recently developed genomic sequencing technique with Taq polymerase. We analyzed seven potential methylation sites between position -460 and -275 of the PAD promoter. Three of the CpG dinucleotides we analyzed are located in the flanking regions of the AP-1 binding site and heat-shock response element consensus sequences. Of the seven CpG dinucleotides present in this region, we found none to be methylated. This finding indicates that, in healthy brain tissue, cytosine methylation of this binding motif seems not to affect protein/DNA interaction. However, it remains to be determined whether methylation of these sites is significant in AD patients.
Milici
A
A
University of Texas M.D. Anderson Cancer Center, Houston 77030.
Salbaum
J M
JM
Beyereuther
K
K
D000544:Alzheimer Disease / Q000235:genetics*; D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase; D005784:Gene Amplification; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D019914:Taq Polymerase
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors; D019914:Taq Polymerase; D004259:DNA-Directed DNA Polymerase