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e2f1 Gene is a new member of Wnt/beta-catenin/Tcf-regulated genes

Maria V Abramova1, Evgeny A Zatulovskiy, Svetlana B Svetlikova

  • 1Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av 4, 194064 St Petersburg, Russia. mav_2004@mail.ru

Biochemical and Biophysical Research Communications
|November 11, 2009
PubMed

Insights

Histone deacetylase inhibitors down-regulate e2f1 gene expression via the Wnt/Tcf pathway. This study demonstrates that e2f1 is a target gene of the Wnt/beta-catenin/Tcf signaling pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Histone deacetylase (HDAC) inhibitors trigger cell cycle arrest in transformed cells.
  • This arrest is associated with decreased e2f1 gene expression and Wnt pathway activation.

Purpose of the Study:

  • To investigate the regulatory mechanism of e2f1 gene expression.
  • To determine if e2f1 is regulated by the Wnt/Tcf pathway.

Main Methods:

  • Analysis of e2f1 promoter activity using luciferase reporter assays.
  • DNA-binding assays to identify Tcf-binding elements in the e2f1 promoter.
  • Treatment with sodium butyrate (NaB) and overexpression of beta-catenin/Tcf.

Main Results:

  • Sodium butyrate (NaB) and beta-catenin/Tcf overexpression inhibited e2f1 promoter activity.
  • Two putative Tcf-binding elements were identified in the e2f1 promoter.
  • The proximal Tcf-binding element mediated positive transcriptional regulation in response to Wnt pathway activation.

Conclusions:

  • E2f1 gene expression is directly regulated by the Wnt/beta-catenin/Tcf signaling pathway.
  • This finding establishes e2f1 as a novel target gene within the Wnt signaling network.

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