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The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

Mathias Jenal1, Emmanuelle Trinh, Christian Britschgi

  • 1Department of Clinical Research, University of Bern, Switzerland.

Molecular Cancer Research : MCR
|June 4, 2009
PubMed

Insights

The Hypermethylated in Cancer 1 (HIC1) gene is a novel transcriptional target of E2F1. E2F1 activation increases HIC1 expression, even in hypermethylated promoters, playing a role in DNA damage responses.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The Hypermethylated in Cancer 1 (HIC1) gene is a tumor suppressor and a transcriptional target of p53.
  • Identifying other regulators of HIC1 is crucial for understanding its role in cancer development.

Purpose of the Study:

  • To identify novel transcriptional regulators of the HIC1 gene.
  • To investigate the role of E2F1 in regulating HIC1 expression and its potential involvement in DNA damage responses.

Main Methods:

  • Screening of transcription factors using a human HIC1 promoter reporter assay.
  • Promoter deletion and mutation analyses to identify E2F responsive elements.
  • Chromatin immunoprecipitation (ChIP) assays to confirm in vivo binding of E2F1 to the HIC1 promoter.
  • Analysis of HIC1 expression in response to E2F1 activation and DNA damage induction.

Main Results:

  • E2F1 strongly activates the HIC1 promoter, with two E2F responsive elements identified in the core promoter region.
  • E2F1 binds to the HIC1 promoter in vivo, leading to increased HIC1 expression, even in hypermethylated regions.
  • Etoposide-induced DNA damage increases E2F1 binding to the HIC1 promoter and enhances HIC1 expression.
  • Inhibition of E2F1 reduces etoposide-induced HIC1 expression.

Conclusions:

  • HIC1 is identified as a novel transcriptional target of E2F1.
  • E2F1 plays a significant role in regulating HIC1 expression, particularly in the context of DNA damage responses.
  • These findings contribute to understanding the complex regulatory network of HIC1 in cancer suppression.

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