Journal
NATURE
Volume 502, Issue 7469, Pages 59-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12593
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Funding
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- MODHEP project
- Israel Science Foundation
- Wellcome Trust
- BBSRC [BBS/E/B/0000C151, BBS/E/B/000C0404] Funding Source: UKRI
- MRC [G117/530, G0800036] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151, BBS/E/B/000C0404] Funding Source: researchfish
- Medical Research Council [G117/530, G0800036] Funding Source: researchfish
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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.
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