Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture

Nat Genet. 2018 May;50(5):754-763. doi: 10.1038/s41588-018-0111-2. Epub 2018 Apr 26.


Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments. Notably, random ligation could be quickly evaluated in an early quality-control step before sequencing. Moreover, an in situ version of DLO Hi-C using a four-cutter restriction enzyme has been developed. We applied DLO Hi-C to delineate the genomic architecture of THP-1 and K562 cells and uncovered chromosomal translocations. This technology may facilitate investigation of genomic organization, gene regulation, and (meta)genome assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotin / genetics
  • Cell Line, Tumor
  • Chromosomes / metabolism*
  • Cost-Benefit Analysis / methods*
  • DNA / genetics
  • Genome / genetics
  • Genomics / methods*
  • Humans
  • K562 Cells
  • Translocation, Genetic / genetics


  • Biotin
  • DNA