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MYC reshapes CTCF-mediated chromatin architecture in prostate cancer

Zhao Wei1, Song Wang2,3,4, Yaning Xu2,3,4

  • 1Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China.

Nature Communications
|March 30, 2023
PubMed

Insights

MYC oncogene rewires prostate cancer chromatin architecture by interacting with CTCF protein, altering genome organization. This interaction disrupts gene looping, impacting cancer cell plasticity.

Area of Science:

  • Cancer Biology
  • Epigenetics
  • Genomics

Background:

  • MYC is a known oncogene in prostate cancer.
  • CTCF protein is crucial for 3D genome organization.
  • The functional link between MYC and CTCF was previously unknown.

Purpose of the Study:

  • To investigate the functional relationship between MYC and CTCF in prostate cancer.
  • To understand how MYC influences chromatin architecture mediated by CTCF.

Main Methods:

  • Utilized H3K27ac, AR, and CTCF HiChIP profiling.
  • Employed CRISPR technology to delete a CTCF binding site near the MYC gene.
  • Analyzed changes in CTCF-mediated chromatin looping upon MYC activation.

Main Results:

  • MYC interacts with CTCF, altering prostate cancer chromatin architecture.
  • MYC enhances CTCF occupancy at specific genomic sites.
  • MYC activation potentiates CTCF-mediated looping, disrupting enhancer-promoter interactions at neuroendocrine lineage plasticity genes.

Conclusions:

  • MYC acts as a co-factor for CTCF in 3D genome organization.
  • This interaction plays a role in prostate cancer progression and lineage plasticity.

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