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The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in

Julie Wells1, Miguel N Rivera, Woo Jae Kim

  • 1Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, USA.

Molecular Cancer Research : MCR
|June 24, 2010
PubMed

Insights

The Wilms

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Wilms' Tumor gene WT1 encodes a tumor suppressor.
  • The prevalent WT1(+KTS) isoform's function is largely unknown.
  • WT1(+KTS) has a disrupted DNA binding domain due to a KTS insertion.

Purpose of the Study:

  • Identify WT1(+KTS)-regulated genes.
  • Investigate the role of WT1(+KTS) in transcriptional regulation.
  • Explore the link between WT1 and planar cell polarity.

Main Methods:

  • Conditional WT1(+KTS) expression in cells.
  • Genome-wide chromatin immunoprecipitation and cloning.
  • Analysis of gene expression patterns and promoter binding.

Main Results:

  • Identified Scribble (SCRB) as the first WT1(+KTS) target gene.
  • WT1 and SCRB expression overlap in developing renal glomeruli.
  • WT1(+KTS) binds to the Scribble promoter in kidney cells.

Conclusions:

  • WT1(+KTS) isoform plays a role in transcriptional regulation.
  • WT1 pathway is linked to the planar cell polarity pathway.
  • Scribble is a key target gene regulated by WT1(+KTS) in the kidney.

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