A novel target for the Wilms' tumour suppressor protein (WT1) is bound by a unique combination of zinc fingers

M H Little, G Holmes, L Pell, A A Caricasole, Antonio Duarte, M Law, A Ward, B Wainwright

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

All isoforms of the Wilms' tumour suppressor protein, WT1, contain four consecutive zinc fingers which facilitate DNA binding. The predominant WT1 transcript contains a 9 base pair insertion resulting in an additional three amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. WT1 zinc fingers 2, 3 and 4 are highly homologous to the zinc fingers of the early growth response gene, EGR1. However, only WT1--KTS is capable of binding an EGR1 consensus site. In contrast, the previously described genomic fragment, +P5 (D1S3309E), is bound by both WT1--KTS and WT1 + KTS. In this study, the region within + P5 to which both WT1 -- KTS and WT1 + KTS bind was defined as 5'-GGAGAGGGAGGATC-3'. EGR1 did not bind + P5. By creating zinc finger deletions, we demonstrate that zinc finger 1, but not zinc finger 4, is critical for + P5 binding; whereas zinc finger 4, but not 1, is necessary for the binding of WT1 target sites within EGR1, PDGF A chain and IGF2 promoters. Thus, zinc finger usage can vary with target and + P5 may represent a novel type of WT1 binding site, the physiological relevance of which must be investigated.

Original languageEnglish
Pages (from-to)1461-9
Number of pages9
JournalOncogene
Volume13
Issue number7
Publication statusPublished - 3 Oct 1996

Keywords

  • Binding Sites
  • DNA
  • DNA-Binding Proteins
  • Molecular Sequence Data
  • Nucleotides
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins
  • Transcription Factors
  • WT1 Proteins
  • Zinc Fingers
  • Journal Article
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Little, M. H., Holmes, G., Pell, L., Caricasole, A. A., Duarte, A., Law, M., Ward, A., & Wainwright, B. (1996). A novel target for the Wilms' tumour suppressor protein (WT1) is bound by a unique combination of zinc fingers. Oncogene, 13(7), 1461-9.