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Oncogene-mediated alterations in chromatin conformation.

David S Rickman1, T David Soong, Benjamin Moss

  • 1Department of Pathology and Laboratory Medicine, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 23, 2012
PubMed
Summary

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Overexpressing the ERG oncogene globally alters prostate cancer cell chromatin organization, impacting gene regulation. This finding has implications for understanding various cancers driven by aberrant transcription factors.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Emerging evidence indicates that the 3D topology of chromatin influences gene transcription.
  • The impact of cancer-related chromatin conformation changes and oncogenic transcription factors on gene regulation remains unclear.

Purpose of the Study:

  • To investigate how overexpression of the ERG oncogenic transcription factor affects global chromatin topology.
  • To understand the relationship between ERG binding, chromatin organization, and gene expression in prostate cancer.

Main Methods:

  • High-resolution mapping of intra- and interchromosome interactions using chromosome conformation capture (Hi-C).
  • Integration of Hi-C data with ERG binding and gene expression data.
  • Analysis of chromatin organization changes upon ERG overexpression.

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Main Results:

  • Oncogenic transcription factor (ERG) overexpression induces global, reproducible changes in chromatin organization.
  • These topological alterations are functionally coherent and linked to gene expression changes.
  • Demonstrated a direct link between ERG activity and large-scale chromatin restructuring.

Conclusions:

  • Oncogenic transcription factor overexpression can globally remodel chromatin topology, affecting gene regulation in cancer.
  • Findings provide insights into cancer mechanisms driven by aberrant transcription factors like ERG, EWS-FLI1, c-Myc, n-Myc, and PML-RARα.