Transactivation of the WT1 antisense promoter is unique to the WT1[+/−] isoform

FEBS Letters

Brown, Keith W.¹  Hall, Julie¹  Moorwood, Kim¹  Salpekar, Ashreena¹  Ivins, Sarah M.¹  Malik, Karim¹  Powlesland, Rachel M.¹ 

[1] CLIC research unit, Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK

关键词: Wilms’ tumour suppressor gene;    Transcription factor;    Antisense RNA;   

DOI  :  10.1016/S0014-5793(99)00944-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown