Principles of Chromosome Architecture Revealed by Hi-C

Trends Biochem Sci. 2018 Jun;43(6):469-478. doi: 10.1016/j.tibs.2018.03.006. Epub 2018 Apr 21.


Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states.

Keywords: DNA loops; Hi-C; chromosome conformation capture; chromosome structure; nuclear compartments; topologically associating domains.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Chromosome Mapping*
  • Chromosomes / chemistry*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Nucleic Acid Conformation