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Chromatin

Mapping genome-wide chromosome interactions

Nature Reviews Genetics volume 10, pages 816–817 (2009)Cite this article

Lieberman-Aiden et al. created a Hi-C library from a karyotypically normal human lymphoblastoid cell line by crosslinking chromatin in the cells, restriction digesting the DNA, adding a biotin tag to the ends of the fragments and then ligating under conditions that favoured ligation between crosslinked fragments that were originally close to each other in the nucleus. The library can be analysed by selecting the biotinylated interacting fragments with streptavidin beads, then massively parallel DNA sequencing the ligated pairs to yield a catalogue of interacting fragments. The authors generated millions of read pairs that could be uniquely aligned to the human genome reference sequence.

The Hi-C data were consistent with known features of genome organization, such as the presence of chromosome territories (the propensity for distant loci that are on the same chromosome to be close to each other in the nucleus) and the tendency of small gene-rich chromosomes to be near each other. They also characterized a higher level of genome organization in which the whole genome can be partitioned into two compartments, with greater interaction occurring within each compartment, rather than across the two compartments. Lieberman-Aiden et al. then examined whether the two compartments correlated with any known genetic or epigenetic features and found that one compartment was associated with open, actively transcribed chromatin, whereas the other correlated with closed chromatin.

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References

ORIGINAL RESEARCH PAPER

  1. Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009)

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FURTHER READING

  1. Lanctôt, C., Cheutin, T., Cremer, M., Cavalli, G. & Cremer, T. et al. Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Rev. Genet. 8, 104–115 (2007)

    Article  Google Scholar 

  2. Dekker, J. Gene regulation in the third dimension. Science 319, 1793–1794 (2008)

    Article  CAS  Google Scholar 

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Authors
  1. Meera Swami
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Swami, M. Mapping genome-wide chromosome interactions. Nat Rev Genet 10, 816–817 (2009). https://doi.org/10.1038/nrg2701

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