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

Tim J. Stevens, David Lando, Srinjan Basu, Liam P. Atkinson, Yang Cao, Steven F. Lee, Martin Leeb, Kai J. Wohlfahrt, Wayne Boucher, Aoife O’Shaughnessy-Kirwan, Julie Cramard, Andre J. Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G. S. Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman and Ernest D. Laue ()
Additional contact information
Tim J. Stevens: University of Cambridge
David Lando: University of Cambridge
Srinjan Basu: University of Cambridge
Liam P. Atkinson: University of Cambridge
Yang Cao: University of Cambridge
Steven F. Lee: University of Cambridge
Martin Leeb: Wellcome Trust – MRC Stem Cell Institute, University of Cambridge
Kai J. Wohlfahrt: University of Cambridge
Wayne Boucher: University of Cambridge
Aoife O’Shaughnessy-Kirwan: University of Cambridge
Julie Cramard: Wellcome Trust – MRC Stem Cell Institute, University of Cambridge
Andre J. Faure: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Meryem Ralser: Wellcome Trust – MRC Stem Cell Institute, University of Cambridge
Enrique Blanco: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Lluis Morey: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Miriam Sansó: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Matthieu G. S. Palayret: University of Cambridge
Ben Lehner: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Luciano Di Croce: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG)
Anton Wutz: Wellcome Trust – MRC Stem Cell Institute, University of Cambridge
Brian Hendrich: University of Cambridge
Dave Klenerman: University of Cambridge
Ernest D. Laue: University of Cambridge

Nature, 2017, vol. 544, issue 7648, 59-64

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature21429

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