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3D GENOMICS

Expanding the toolbox for 3D genomics

Nature Genetics volume 50, pages 634–635 (2018)Cite this article

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The ability to visualize and study the 3D folding of chromosomes in cells has been propelled forward by several major technological advances in the past two decades. Two new studies now further expand the scientific toolbox for studying chromosome conformation by providing novel methodologies for accurate mapping of genome topology and predicting the topological effects of genomic structural variation.

Evaluating how chromatin is organized in the 3D nuclear space is rapidly becoming an integral part of studies into various DNA-templated processes, such as transcription, replication and recombination. Taking a step back, one comes to realize just how rapidly the field has transitioned from microscopy-based approaches limited in resolution and throughput to a powerful combination of genomics, microscopy and computational technologies that is able to paint a high-resolution multiscale picture of chromatin architecture1. Through this technological revolution, spearheaded by development of the chromosome conformation capture (3C) method by Dekker et al.2, chromosomes are now considered to fold into active (A) and inactive (B) compartments that are partitioned into smaller topologically associating domains (TADs) and chromatin loops. Moreover, genome topology is considered to have important roles in the regulation of gene expression, DNA replication, X-chromosome inactivation, adaptive immunity and cell fate decisions3,4,5,6. Importantly, recent studies have shown that abnormal chromatin folding can lead to disease, including developmental disorders and cancer7,8. Although improved protocols for 3C and its derivatives have made this technology far more accessible, data generation—in particular for the genome-wide Hi-C variant—is still challenging and costly. Moreover, it remains difficult to predict how complex changes to mammalian genomes (for example, the large structural alterations often present in human disorders) impact chromatin architecture and subsequent gene regulatory processes. In this issue, studies by Lin et al.9 and Bianco et al.10 introduce new methodologies that promise to further facilitate the generation and functional interpretation of genome-wide chromatin interaction maps.

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Fig. 1: New methodology for measuring (DLO Hi-C) and modeling (PRISMR) the 3D genome.

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands

    Ralph Stadhouders

  2. Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands

    Ralph Stadhouders

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  1. Ralph Stadhouders
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Correspondence to Ralph Stadhouders.

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Stadhouders, R. Expanding the toolbox for 3D genomics. Nat Genet 50, 634–635 (2018). https://doi.org/10.1038/s41588-018-0112-1

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