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

Weihong Song, Debomoy K. Lahiri

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Abnormal regulation of transcription of the β-amyloid precursor protein (βAPP) 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 βAPP gene of the Rhesus monkey (rhβAPP). 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-κB. The sequence of the rhβAPP promoter also contains several sites for the binding of proteins that serve as signal transducers and activators of transcription (STAT1) (GAS). The rhβAPP 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 βAPP 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.

Original languageEnglish (US)
Pages (from-to)151-164
Number of pages14
JournalGene
Volume217
Issue number1-2
DOIs
StatePublished - Sep 14 1998

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • APP promoter
  • Gene regulation
  • Genomic screening
  • Primate
  • Primer extension
  • S1 nuclease mapping
  • Transcription factor

ASJC Scopus subject areas

  • Genetics

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