Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions

Sci Rep. 2017 May 19;7(1):2186. doi: 10.1038/s41598-017-02257-3.

Abstract

Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes. Besides cell lines, we could observe chromatin interactions by a Chromosome Conformation Capture (3C)-based method, in primary human samples. Several chromatin interactions involving super-enhancers and broad H3K4me3 domains are constitutive and can be found in both cancer and normal samples. Taken together, these results reveal a new layer of complexity in gene regulation by super-enhancers and broad H3K4me3 domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics*
  • Chromatin / metabolism*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Protein Interaction Domains and Motifs*

Substances

  • Chromatin
  • Histones
  • Multiprotein Complexes