Molecular cloning of the promoter of the gene encoding the Rhesus monkey β-amyloid precursor protein:: structural characterization and a comparative study with other species

Abnormal regulation of transcription of the beta-amyloid precursor protein (beta APP) gene is implicated in the pathogenesis of Alzheimer's disease (AD). We have examined a 17- kb genomic DNA region which contains the 5'-flanking region (promoter), first exon and intron of the beta APP gene of the Rhesus monkey (rh beta APP). A predominant transcription start site was identified 146 bp upstream of the translation initiation codon. Sequencing of 5848 bp of 5'-flanking DNA revealed the presence of multiple near consensus sequences for binding potential transcriptional regulatory factors, such as activator proteins (AP-1, AP-2), an apolipoprotein E-B1 element, estrogen-responsive element, heat shock element and NF-kappa B. The sequence of the rh beta APP promoter also contains several sites for the binding of proteins that serve as signal transducers and activators of transcription (STAT1) (GAS). The rh beta APP promoter is highly homologous to the human promoter, but less homologous to the rodents. The homology between human and Rhesus monkey of the further upstream region gradually decreased over its length. A region of 270 bp of the human beta APP promoter is missing from the Rhesus monkey promoter. Structural analysis of the promoter suggests that it contains characteristics of inducible genes and sites for regulated activity by various transcription factors. (C) 1998 Elsevier Science B.V. All rights reserved.