THE RAT AMYLOID PRECURSOR PROTEIN PROMOTER CONTAINS 2 DNA REGULATORY ELEMENTS WHICH INFLUENCE HIGH-LEVEL GENE-EXPRESSION

We have investigated the transcriptional activity and regulatory elements of the rat amyloid precursor protein promoter. A DNA fragment containing 375 base pairs upstream of the start codon drives transcription in rat PC12 cells at a level greater than five-fold that of the SV40 promoter. This fragment contains a predominant transcription start point and several additional start points which are similar to those found in the human promoter. The strong promoter activity appears to be dependent upon two small DNA regulatory elements. Deletion of one element at positions -260 through -248 reduces activity by 85%. This is the first report of a positive regulatory element at this location. Deletion of a second element at positions -223 through -192 reduces activity by 30%. Gel mobility shift assays with nuclear extracts from whole rat brain suggest that nuclear proteins interact directly with the second element but not with the first one. (C) 1994 Academic Press, Inc.