title: Transactivation of the WT1 antisense promoter is unique to the WT1[+/-] isoform.
abstract: The Wilms' tumour suppressor gene, WT1, encodes a zinc finger transcription factor that has been shown to repress a variety of cellular promoters via binding to cognate DNA elements. Our earlier work identified an antisense WT1 promoter that contains WT1 consensus sites, but is transcriptionally activated by WT1. In this study, we demonstrate that, unlike previous reports of transcriptional regulation by WT1, transactivation of the antisense promoter is unique to a single isoform of WT1. Of the four alternatively spliced isoforms in which exon 5 (at splice I) or amino acid residues KTS (at splice II) are inserted or omitted, only the WT1 isoform containing splice I and omitting splice II (WT1[+/-]) displays transactivation. We demonstrate that transregulation variations observed with WT1 isoforms are not solely attributable to differential DNA binding by [+KTS] or [-KTS] isoforms. Thus, the transactivation of the antisense promoter displays an absolute requirement for exon 5, suggesting that interaction between WT1 and other cellular factors is necessary for this regulatory function.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, UK. k.moorwood@bris.ac.uk
authors.forename: K
authors.initials: K
authors.lastname: Moorwood
authors.forename: A
authors.initials: A
authors.lastname: Salpekar
authors.forename: S M
authors.initials: SM
authors.lastname: Ivins
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: R M
authors.initials: RM
authors.lastname: Powlesland
authors.forename: K W
authors.initials: KW
authors.lastname: Brown
authors.forename: K
authors.initials: K
authors.lastname: Malik
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D016373:DNA, Antisense / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D025721:WT1 Proteins
chemical_list: D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D025721:WT1 Proteins; D004247:DNA