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

• Published in: Nature genetics Vol. 50; no. 5; pp. 754 - 763
• Main Authors: Lin, Da, Hong, Ping, Zhang, Siheng, Xu, Weize, Jamal, Muhammad, Yan, Keji, Lei, Yingying, Li, Liang, Ruan, Yijun, Fu, Zhen F., Li, Guoliang, Cao, Gang
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-05-2018; Nature Publishing Group
• Subjects: 45; 45/23; 45/77; 631/1647/2217; 631/208; 631/208/212; Agriculture; Animal Genetics and Genomics; Background noise; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Biotin; Biotin - genetics; Cancer Research; Cell Line, Tumor; Chromosome translocations; Chromosomes; Chromosomes - metabolism; Conformation; Cost-Benefit Analysis - methods; Costs; Deoxyribonucleic acid; Digestion; DNA; DNA - genetics; Enzymes; Gene expression; Gene Function; Gene loci; Gene regulation; Genome - genetics; Genomes; Genomics; Genomics - methods; Human Genetics; Humans; Investigations; K562 Cells; Leukemia; Methods; Noise; technical-report; Translocation, Genetic - genetics
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/s41588-018-0111-2

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.
DLO Hi-C is a new method to investigate the 3D genome. It requires only two rounds of digestion and ligation and removes non-ligated DNA in a cost-effective step by purifying specific linker-ligated DNA fragments.