title: A single amino acid change converts an inhibitory transcription factor into an activator.
abstract: The closely related POU family transcription factors Brn-3a and Brn-3b differ in their functional activity with Brn-3a activating several target promoters, which are repressed by Brn-3b. Brn-3b also prevents promoter activation by Brn-3a. Here we have altered a single isoleucine residue in the POU homeodomain of Brn-3b to the valine residue found at the equivalent position in Brn-3a. This change not only abolishes the ability of Brn-3b to repress basal and Brn-3a-stimulated promoter activity but also converts it to an activator of similar potency to Brn-3a. Hence a single amino acid difference determines the difference between an activator and a repressor in the Brn-3 family.
authors.affiliation: Department of Molecular Pathology, University College London Medical School, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dawson
authors.forename: P J
authors.initials: PJ
authors.lastname: Morris
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors