Repression of the transforming growth factor-beta 1 gene by the Wilms' tumor suppressor WT1 gene product

Mol Endocrinol. 1994 May;8(5):595-602. doi: 10.1210/mend.8.5.8058069.


The Wilms' tumor suppressor gene (WT1) encodes a zinc finger DNA binding protein which functions as a transcriptional repressor. In this study we investigated whether the human transforming growth factor-beta 1 (TGF-beta 1) gene might be a target for transcriptional repression mediated by WT1. Using constructs of the TGF-beta 1 promoter linked to the chloramphenicol acetyl transferase gene, we have demonstrated that the WT1 protein represses expression of the TGF-beta 1 gene through a CGCCCCCGC response element spanning nucleotides -111 to -119 of the TGF-beta 1 promoter. We have also shown in a cotransfection assay that Egr-1, an immediate early growth response gene, activates transcription of the TGF-beta 1 gene through the same response element and that WT1 represses both the basal and Egr-1-induced TGF-beta 1 promoter activity in monkey kidney CV-1 cells. Moreover, WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the TGF-beta 1 promoter in gel mobility shift assays. These findings provide further definition of transcriptional control of the TGF-beta 1 gene by showing that the WT1 gene product suppresses TGF-beta 1 transcription and that the WT1/Egr-1 consensus element of the human TGF-beta 1 promoter plays a critical role in this repression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Chlorocebus aethiops
  • Consensus Sequence
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Protein 1
  • Genes, Wilms Tumor*
  • Humans
  • Immediate-Early Proteins*
  • Kidney
  • Mice
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic*
  • Transcription Factors / metabolism
  • Transfection
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Zinc Fingers


  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Immediate-Early Proteins
  • Oligodeoxyribonucleotides
  • Transcription Factors
  • Transforming Growth Factor beta
  • Chloramphenicol O-Acetyltransferase