Single-cell Hi-C reveals cell-to-cell variability in chromosome structure

Takashi Nagano, Yaniv Lubling, Tim J. Stevens, Stefan Schoenfelder, Eitan Yaffe, Wendy Dean, Ernest D. Laue (), Amos Tanay () and Peter Fraser ()
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Takashi Nagano: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK
Yaniv Lubling: Weizmann Institute, Rehovot 76100, Israel
Tim J. Stevens: University of Cambridge, Cambridge CB2 1GA, UK
Stefan Schoenfelder: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK
Eitan Yaffe: Weizmann Institute, Rehovot 76100, Israel
Wendy Dean: Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK
Ernest D. Laue: University of Cambridge, Cambridge CB2 1GA, UK
Amos Tanay: Weizmann Institute, Rehovot 76100, Israel
Peter Fraser: Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK

Nature, 2013, vol. 502, issue 7469, 59-64

Abstract: Abstract Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X chromosomes, to show that individual chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell chromosome structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organization underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns.

Date: 2013
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DOI: 10.1038/nature12593

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