Genomic retargeting of p53 and CTCF is associated with transcriptional changes during oncogenic HRas-induced

Michal Schwartz1,2, Avital Sarusi Portugez1, Bracha Zukerman Attia1

  • 1The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Communications Biology
|November 26, 2020
PubMed

Insights

Cancer development involves changes in gene regulation. This study reveals how transcription factors p53 and CTCF alter gene expression during early oncogene-induced transformation, highlighting the role of regulatory elements in cancer progression.

Area of Science:

  • Genomics
  • Epigenetics
  • Cancer Biology

Background:

  • Gene transcription is controlled by regulatory elements and transcription factors.
  • Changes in chromatin and transcription factor binding at regulatory elements are implicated in cancer.
  • Understanding early oncogene-induced transformation is crucial for cancer research.

Purpose of the Study:

  • To investigate the regulatory network driving transcriptional changes during early oncogene-induced carcinogenic transformation.
  • To identify key transcription factors and regulatory elements involved in this process.

Main Methods:

  • Utilized Hi-C data to analyze spatial coupling between genes and regulatory elements.
  • Characterized transcription factor binding and chromatin accessibility.
  • Focused on early stages of oncogenic HRas-induced transformation in human mammary epithelial cells.

Main Results:

  • Observed spatial coupling between differentially expressed genes and their regulatory elements.
  • Identified p53 and CTCF as key transcription factors influencing early transcriptional alterations.
  • Demonstrated that malignant transcriptional reprogramming is driven by altered chromatin binding of these factors, not expression level changes.

Conclusions:

  • Alterations in the regulatory landscape are critical drivers of oncogene-induced transcriptional reprogramming.
  • The redistribution of transcription factor binding, specifically p53 and CTCF, plays a significant role in early cancer development.
  • This study provides insights into the mechanisms underlying oncogenic transformation.

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