Etiology of super-enhancer reprogramming and activation in cancer

Royce W. Zhou, Ramon E. Parsons

Research output: Contribution to journalReview articlepeer-review

Abstract

Super-enhancers are large, densely concentrated swaths of enhancers that regulate genes critical for cell identity. Tumorigenesis is accompanied by changes in the super-enhancer landscape. These aberrant super-enhancers commonly form to activate proto-oncogenes, or other genes upon which cancer cells depend, that initiate tumorigenesis, promote tumor proliferation, and increase the fitness of cancer cells to survive in the tumor microenvironment. These include well-recognized master regulators of proliferation in the setting of cancer, such as the transcription factor MYC which is under the control of numerous super-enhancers gained in cancer compared to normal tissues. This Review will cover the expanding cell-intrinsic and cell-extrinsic etiology of these super-enhancer changes in cancer, including somatic mutations, copy number variation, fusion events, extrachromosomal DNA, and 3D chromatin architecture, as well as those activated by inflammation, extra-cellular signaling, and the tumor microenvironment.

Original languageEnglish
Article number29
JournalEpigenetics and Chromatin
Volume16
Issue number1
DOIs
StatePublished - Dec 2023

Keywords

  • Cancer
  • Enhancers
  • Extrachromosomal DNA
  • Inflammation
  • Insulators
  • Non-coding mutations
  • Phase separation
  • Super-enhancers
  • Therapeutic resistance
  • Topologically associated domain
  • Tumor microenvironment

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