title: Activation and repression of prion protein expression by key  regions of intron 1.
abstract: Expression of the prion protein is necessary for infection with prion diseases. Altered expression levels may play an important role in susceptibility to infection. Therefore, understanding the mechanisms that regulate prion protein expression is of great importance. It was previously shown that expression of the prion protein is to some degree regulated by an alternative promoter within intron 1. Studies using GFP and luciferase reporter systems were undertaken to determine key sites for the repression and activation of expression of the prion protein driven by intron 1. We identified a region within intron 1 sufficient to drive prion protein expression. Our findings highlight two potential repressor regions. Both regions have binding sites for the known repressor Hes-1. Hes-1 overexpression caused a dramatic decrease in PrP protein expression. Additionally, we have identified Atox-1 as a transcription factor that upregulates prion protein expression. These findings clearly indicate that intron 1 plays a key role in regulation of prion protein expression levels.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Wright
authors.forename: Patrick C
authors.initials: PC
authors.lastname: McHugh
authors.forename: Mark
authors.initials: M
authors.lastname: Stockbridge
authors.forename: Samantha
authors.initials: S
authors.lastname: Lane
authors.forename: Silvia
authors.initials: S
authors.lastname: Kralovicova
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D000818:Animals; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000502:physiology*; D002460:Cell Line; D000079922:Copper Transport Proteins; D005786:Gene Expression Regulation; D007438:Introns; D051379:Mice; D018832:Molecular Chaperones / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016385:TATA Box
chemical_list: C499247:Atox1 protein, mouse; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D018832:Molecular Chaperones; D011328:Prions