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Updated: Nov 28, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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.
Abstract:
Gene transcription is regulated by distant regulatory elements via combinatorial binding of transcription factors. It is increasingly recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene-induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional changes associated with this process. Using Hi-C data, we observe spatial coupling between differentially expressed genes and their differentially accessible regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as determinants of transcriptional alterations at the early stages of oncogenic HRas-induced transformation in human mammary epithelial cells. Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.
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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