3D structure of individual mammalian genomes studied by single cell Hi-C
Di Croce, L
Nature Publishing Group
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Stevens, T., Lando, D., Basu, S., Atkinson, L., Cao, Y., Lee, S., Leeb, M., et al. (2017). 3D structure of individual mammalian genomes studied by single cell Hi-C. Nature https://doi.org/10.1038/nature21429
The folding of genomic DNA from the beads-on-a-string like structure of nucleosomes into higher order assemblies is critically linked to nuclear processes. We have calculated the first 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. This has allowed us to study genome folding down to a scale of <100 kb and to validate the structures. We show that the structures of individual topological-associated domains and loops vary very substantially from cell-to-cell. By contrast, A/B compartments, lamin-associated domains and active enhancers/promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. Through studying pluripotency factor- and NuRD-regulated genes, we illustrate how single cell genome structure determination provides a novel approach for investigating biological processes.
We thank the Wellcome Trust (082010/Z/07/Z), the EC FP7 4DCellFate project (277899) and the MRC (MR/M010082/1) for financial support.
Wellcome Trust (082010/Z/07/Z)
EC FP7 CP (277899)
Wellcome Trust (206291/Z/17/Z)
External DOI: https://doi.org/10.1038/nature21429
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262894