Oncogene-mediated alterations in chromatin conformation Academic Article uri icon

Overview

MeSH Major

  • Chromatin Assembly and Disassembly
  • Nucleic Acid Conformation
  • Trans-Activators

abstract

  • Emerging evidence suggests that chromatin adopts a nonrandom 3D topology and that the organization of genes into structural hubs and domains affects their transcriptional status. How chromatin conformation changes in diseases such as cancer is poorly understood. Moreover, how oncogenic transcription factors, which bind to thousands of sites across the genome, influence gene regulation by globally altering the topology of chromatin requires further investigation. To address these questions, we performed unbiased high-resolution mapping of intra- and interchromosome interactions upon overexpression of ERG, an oncogenic transcription factor frequently overexpressed in prostate cancer as a result of a gene fusion. By integrating data from genome-wide chromosome conformation capture (Hi-C), ERG binding, and gene expression, we demonstrate that oncogenic transcription factor overexpression is associated with global, reproducible, and functionally coherent changes in chromatin organization. The results presented here have broader implications, as genomic alterations in other cancer types frequently give rise to aberrant transcription factor expression, e.g., EWS-FLI1, c-Myc, n-Myc, and PML-RARα.

publication date

  • June 5, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3384175

Digital Object Identifier (DOI)

  • 10.1073/pnas.1112570109

PubMed ID

  • 22615383

Additional Document Info

start page

  • 9083

end page

  • 8

volume

  • 109

number

  • 23