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Cell density-dependent nuclear accumulation of ELK3 is involved in suppression of PAI-1 expression

Shu Tanaka1, Kazuyuki Nakao, Toshihiro Sekimoto

  • 1Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Yamada-oka, Suita, Osaka, Japan.

Cell Structure and Function
|May 28, 2013
PubMed

Insights

Cell density impacts gene expression. High cell density causes transcription factor ELK3 to repress plasminogen activator inhibitor type 1 (PAI-1) expression by binding to its promoter, inhibiting cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Transcription Factor Regulation

Background:

  • Cell-cell contact influences cell proliferation and differentiation.
  • The dynamic behavior of transcription factors during cell density changes is not well understood.

Purpose of the Study:

  • To investigate the role of transcription factors in cell-density-dependent gene expression.
  • To elucidate the mechanism by which ELK3 regulates plasminogen activator inhibitor type 1 (PAI-1) expression.

Main Methods:

  • Quantitative analysis of mRNA levels.
  • Investigation of transcription factor localization and DNA binding.
  • Promoter analysis to identify binding sites.

Main Results:

  • Plasminogen activator inhibitor type 1 (PAI-1) mRNA levels decrease at high cell density.
  • ELK3 represses PAI-1 expression and accumulates in the nucleus at high cell density.
  • ETS1, a PAI-1 activator, is displaced from the PAI-1 promoter at high cell density, while ELK3 binds.

Conclusions:

  • A transcription factor switch from ETS1 to ELK3 occurs at the PAI-1 promoter with increasing cell density.
  • This switch leads to the suppression of PAI-1 expression, contributing to cell-density-dependent growth regulation.

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