A high-resolution map of the three-dimensional chromatin interactome in human cells

Nature. 2013 Nov 14;503(7475):290-4. doi: 10.1038/nature12644. Epub 2013 Oct 20.

Abstract

A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

Publication types

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

MeSH terms

  • Cell Line
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromosome Mapping*
  • Enhancer Elements, Genetic / physiology
  • Gene Expression Regulation
  • Genome, Human*
  • Humans
  • Imaging, Three-Dimensional
  • Promoter Regions, Genetic / physiology
  • Protein Binding
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chromatin
  • Tumor Necrosis Factor-alpha

Associated data

  • GEO/GSE43070