The promoter of Alzheimer's disease amyloid A4 precursor gene.
The promoter of the gene for the precursor of Alzheimer's Disease A4 amyloid protein (PAD gene) resembles promoters of housekeeping genes. A typical TATA box is missing, and transcription initiates at multiple sites. It shows a high GC content of 72% in a DNA region that confers promoter activity to a reporter gene in vivo. Upstream of the RNA start sites we found sequences homologous to the consensus binding sites of transcription factor AP-1 and the heat shock control element binding protein. Six copies of a 9bp long GC-rich element are located between positions -100 and -200 of the sequence. A protein-DNA interaction could be mapped to this element. The ratio of the dinucleotide CpG, the target for DNA methylation, versus GpC is about 1:1 around the RNA start site, in contrast to the normal ratio of 1:5 in eucaryotic DNA. These findings suggest that four mechanisms may participate in the regulation of the PAD gene: the stress-related heat shock; the AP-1/Fos binding; the GC-rich element, and the possible methylation of the CpG region. PAD gene regulation could be of relevance for the progression of amyloid deposition in Alzheimer's Disease.
Salbaum
J M
JM
Center for Molecular Biology, University of Heidelberg, F.R. Germany.
Weidemann
A
A
Masters
C L
CL
Beyreuther
K
K
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000682:Amyloid / Q000235:genetics*; D016229:Amyloid beta-Peptides; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014158:Transcription, Genetic
D000682:Amyloid; D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins