Isolation and functional characterisation of the promoter region of the human prion protein gene

The human prion protein gene (PRNP) encodes a 33-35 kDa cell surface protei n that is highly expressed in the central nervous system and is vital to th e pathogenesis of prion diseases. We have characterised the promoter region of PRNP as a first step towards defining the mechanisms regulating its exp ression. Sequence analysis of a 2.7 kb genomic DNA fragment containing exon I and the 5 ' -flanking region of PRNP, revealed a number of putative tran scriptional factor binding sites, including Sp1, Ap-1, Ap-2 and a CCAAT box . Transient transfection assays in tissue culture cells with constructs con sisting of the wild-type and deletion mutants of the PRNP 2.7 kb genomic fr agment driving a luciferase reporter gene, demonstrate an active promoter w ithin a 273 bp region (-148 to + 125, relative to the cap site). (C) 2001 P ublished by Elsevier Science B.V. All rights reserved.