Cited by 1,589Genomics and Chromatin DynamicsGenomic variations and chromosomal abnormalitiesNuclear Structure and Function

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

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Nagano, Takashi, Lubling, Yaniv, Stevens, Tim J., Schoenfelder, Stefan, Yaffe, Eitan, Dean, Wendy, Laue, Ernest D., Tanay, Amos, Fraser, Peter·2013·Nature

DOI 10.1038/nature12593PMC PMC3869051

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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.

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Authors: Nagano, T., Lubling, Y., Stevens, T. J., Schoenfelder, S., Yaffe, E., Dean, W., Laue, E. D., Tanay, A., & Fraser, P.
Affiliations: Babraham Institute (GB)
Weizmann Institute of Science (IL)
University of Cambridge (GB)
Corresponding author: Laue, Ernest D.
Tanay, Amos
Fraser, Peter
ORCID: Nagano, Takashi
Lubling, Yaniv
Stevens, Tim J.
Schoenfelder, Stefan
Yaffe, Eitan
Dean, Wendy
Laue, Ernest D.
Tanay, Amos
Fraser, Peter
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-09-25
Volume: 502
Issue: 7469
Pages: 59-64
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12593
PMC: PMC3869051
OpenAlex: W1965863160
Cited by: 1,589
References: 32
Citations by year: 2026: 75 · 2025: 100 · 2024: 118 · 2023: 115 · 2022: 120 · 2021: 177 · 2020: 132 · 2019: 143 · 2018: 147 · 2017: 126 · 2016: 116 · 2015: 125 · 2014: 86 · 2013: 8
FWCI: 50.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBS/E/B/0000M241, BBS/E/B/000C0404, BBS/E/B/0000C151)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords: single-cell Hi-C, chromosome conformation, cell-to-cell variability, chromosome structure, chromosome territories, X chromosome, 3D genome organization, chromatin interactions, interdomain contacts, nuclear organization
MeSH terms: Animals, Cell Nucleus, Chromatin, Chromosomes, Genetic Techniques, Male, Models, Molecular, Molecular Conformation, X Chromosome, Mice, Single-Cell Analysis

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

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