title: Isolation and functional characterisation of the promoter region of the human prion protein gene.
abstract: The human prion protein gene (PRNP) encodes a 33-35 kDa cell surface protein that is highly expressed in the central nervous system and is vital to the pathogenesis of prion diseases. We have characterised the promoter region of PRNP as a first step towards defining the mechanisms regulating its expression. 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 transcriptional factor binding sites, including Sp1, Ap-1, Ap-2 and a CCAAT box. Transient transfection assays in tissue culture cells with constructs consisting of the wild-type and deletion mutants of the PRNP 2.7 kb genomic fragment driving a luciferase reporter gene, demonstrate an active promoter within a 273 bp region (-148 to +125, relative to the cap site).
authors.affiliation: MRC Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, W2 1PG, London, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Mahal
authors.forename: E A
authors.initials: EA
authors.lastname: Asante
authors.forename: M
authors.initials: M
authors.lastname: Antoniou
authors.forename: J
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005091:Exons; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008322:Mammals / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D018621:PrPC Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018621:PrPC Proteins; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D008156:Luciferases