Journal Article

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

Blanco, Enrique, Laue, Ernest D., Ralser, Meryem, Lee, Steven F., Klenerman, Dave, Basu, Srinjan, Palayret, Matthieu G. S., Lehner, Ben, Morey, Lluis, Stevens, Tim J., Sansó, Miriam, Leeb, Martin, Lando, David, Cao, Yang, Wohlfahrt, Kai J., Hendrich, Brian, Boucher, Wayne, Faure, Andre J., Di Croce, Luciano, Atkinson, Liam P., O’Shaughnessy-Kirwan, Aoife, Wutz, Anton, Cramard, Julie

2017

Overview

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.