Transcriptional regulation of the mouse presenilin-1 gene.

The presenilin-1 (PS-1) gene encodes at least three separate mRNA transcripts from its 12 exons, which are spread over 50 kilobase pairs of mouse DNA. The first transcript begins with exon 1A, whereas the other transcripts begin with exon 1B. Different portions of exon 1B are spliced to give long and short mRNAs. The expression of all of these transcripts depends on a single promoter located just upstream of exon 1A. Although this region lacks a TATA box and a number of common initiator sequences, it does contain a CAAT box, a heat-shock responsive element, a polyomavirus enhancer activator-3 site, an Ets 1-3 site, and multiple-Sp1 and multiple-Ap2 binding sites, which are typically found in eukaryotic promoters. We have combined a reporter gene with various portions of this putative PS-1 promoter and measured firefly luciferase activity relative to an internal renilla luciferase standard. We identified a 25-base pair fragment spanning the 5'-transcription start site of exon 1A as containing the core of the promoter activity. The sequences downstream of this region had undetectable promoter activity, suggesting that this core element is the gene's only promoter, and it controls expression of all three transcripts. Although human PS-1 mRNA expression is clearly different from the mouse PS-1 mRNA pattern, the human and mouse core promoters do share limited homology.