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Nature. 2017 Apr 6;544(7648):59-64. doi: 10.1038/nature21429. Epub 2017 Mar 13.

3D structures of individual mammalian genomes studied by single-cell Hi-C.

Author information

1
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
2
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
3
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
4
Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
5
EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
6
Universitat Pompeu Fabra, 08003 Barcelona, Spain.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
#
Contributed equally

Abstract

The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 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. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell. By contrast, A and B compartments, lamina-associated domains and active enhancers and promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. By studying genes regulated by pluripotency factor and nucleosome remodelling deacetylase (NuRD), we illustrate how the determination of single-cell genome structure provides a new approach for investigating biological processes.

PMID:
28289288
PMCID:
PMC5385134
DOI:
10.1038/nature21429
[Indexed for MEDLINE]
Free PMC Article

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