Super-enhancers in the control of cell identity and disease

Cell. 2013 Nov 7;155(4):934-47. doi: 10.1016/j.cell.2013.09.053. Epub 2013 Oct 10.

Abstract

Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. We produce a catalog of super-enhancers in a broad range of human cell types and find that super-enhancers associate with genes that control and define the biology of these cells. Interestingly, disease-associated variation is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes important in tumor pathogenesis. Thus, super-enhancers play key roles in human cell identity in health and in disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Embryonic Stem Cells / metabolism*
  • Enhancer Elements, Genetic*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • RNA Polymerase II / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Chromatin
  • Transcription Factors
  • RNA Polymerase II