Transcription factor occupancy limits DNA methylation and determines ICAM1 expression in breast cancer

Mingcang Chen1,2, Ying Zhou3, Zhengwei Fu1

  • 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.

Insights

Transcription factor (TF) binding reduces DNA methylation at the ICAM1 promoter, increasing ICAM1 expression in breast cancer. This epigenetic regulation is crucial for understanding TF roles in cancer gene expression.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • The interplay between transcription factor (TF) binding and DNA methylation is vital for gene expression regulation.
  • The specific role of this interaction in ICAM1 (Intercellular Adhesion Molecule 1) expression within breast cancer remains unclear.

Purpose of the Study:

  • To investigate the relationship between TF binding, DNA methylation, and ICAM1 expression in breast cancer.
  • To elucidate the molecular mechanisms underlying ICAM1 regulation in breast cancer.

Main Methods:

  • Correlation analysis of CpG methylation, ICAM1 expression, and DNMT/TET3 levels in breast cancer.
  • Investigating the effect of TF binding on ICAM1 promoter methylation.
  • Analyzing the recruitment of TET3 by transcription factors (RELA, STATs) to the ICAM1 promoter.

Main Results:

  • CpG methylation in the ICAM1 promoter negatively correlates with ICAM1 expression.
  • ICAM1 expression positively correlates with DNA methyltransferase (DNMT) and TET3 expression.
  • TF binding reduces ICAM1 promoter methylation and enhances ICAM1 transcription.
  • RELA and STATs recruit TET3 to inhibit DNMT-mediated methylation, maintaining promoter hypomethylation.

Conclusions:

  • TF occupancy modulates DNA methylation at the ICAM1 promoter, thereby influencing ICAM1 expression in breast cancer.
  • Epigenetic mechanisms involving TF-TET3-DNMT interactions are key regulators of ICAM1 in breast cancer.

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