Dissecting super-enhancer hierarchy based on chromatin interactions

Nat Commun. 2018 Mar 5;9(1):943. doi: 10.1038/s41467-018-03279-9.


Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.

Publication types

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

MeSH terms

  • CCCTC-Binding Factor / metabolism
  • CRISPR-Cas Systems / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • Disease / genetics
  • Enhancer Elements, Genetic*
  • Gene Editing
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Genetic Variation
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • K562 Cells
  • Models, Genetic
  • Protein Binding


  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone