Genomic organization of the human amyloid beta-protein precursor gene

Shun ichi Yoshikai, Hiroyuki Sasaki, Katsumi Doh-ura, Hirokazu Furuya, Yoshiyuki Sakaki

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Amyloid β-protein (BP) deposited in Alzheimer brains is a cleavage product of a larger precursor (BPP). The BPP gene encodes three types of mRNA generated by alternative splicing, two of which contain the sequence encoding Kunitz-type serine-protease inhibitor (serpin). To investigate the regulatory mechanisms of BPP synthesis at the gene level, we isolated 36 genomic DNA clones covering all the exons of the human BPP gene. This gene consists of 18 exons and spans more than 170 kb. BP is encoded by the 16th and the 17th exons and the serpin domain by the 7th exon. Sequence analysis showed that the 7th and 8th introns lack a typical branchpoint for splicing. This might relate to the alternative splicing. The promoter of the BPP gene has some characteristics of those of housekeeping genes and contains a number of possible methylation sites. The methylation status of the promoter was analyzed by Southern blotting but no alteration was observed among tissues and between control and Alzheimer brains. We also tested the roles of two possible activator protein-1-binding sites and a possible heat-shock element found within the promoter. Northern blotting showed that the transcription of the BPP gene was apparently induced by 12-O-tetradecanoylphorbol-13-acetate (phorbol derivative) in HeLa cells.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalGene
Volume87
Issue number2
DOIs
Publication statusPublished - 1990 Mar 15
Externally publishedYes

Keywords

  • Alzheimer's disease
  • DNA methylation
  • Recombinant DNA
  • alternative splicing
  • exon-intron boundary
  • genomic DNA library
  • transcription

ASJC Scopus subject areas

  • Genetics

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