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3D structures of individual mammalian genomes studied by single-cell Hi-C
Open accessAbstract
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.
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“In regard to chromatin structure, Stevens and colleagues reported that the combination of chromosome conformation capture (3C) and tagged fluorescent imaging was able to detect the folding of a genomic sequence <100bp in a single cell (303).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [303]
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“Currently, single-cell Hi-C studies confirm the presence of TADs in individual cells but demonstrate significant variability in their shape (i.e., in the folding of DNA within TADs) [142,143,144,145].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [144]
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Citations
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Self-citationHarmonizing single-cell 3D genome data with STARK and scNucleome
Jiang, W.-J., Cai, K., Yuanchen, S., Liu, A., Zhu, H. P., Gao, R., Zhong, C., Wei, N., Lai, F., Fei, T., et al. (2026) · Genome biology · doi:10.1186/s13059-026-03938-x · Cited by 1
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“Distinct diseases like tumor or metastases may be characterized by specific chromatin modifications and by DNA spatial redistribution in chromatin domain [10], [11].”
BackgroundCRISPR-Based DNA Imaging in Living Cells Reveals Cell Cycle-Dependent Chromosome DynamicsPreprint
Ma, H., Tu, L., Naseri, A., Chung, Y.-C., Grünwald, D., Zhang, S., & Pederson, T. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/195966 · Cited by 1
“that they had been limited to ensemble measurements made on populations of cells, has recently been overcome by refinements that enable singe cell-based analysis (Nagano et al., 2013; Stevens et al., 2017; Flyamer et al., 2017; Nagano et al., 2017).”
MethodAn Introduction to Integrative Genomics and Systems Medicine in Cancer
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“To better understand the genome structure at a higher resolution, single-cell level profiling techniques are urgently needed to accurately capture the variability of chromatin domains [2,3].”
BackgroundPhysical Principles of Retroviral Integration in the Human GenomePreprint
Michieletto, D., Lusic, M., Marenduzzo, D., & Orlandini, E. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/247437 · Cited by 1
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“3D structure reconstruction from a single cell HiC data was developed in [64] based on NMR principle, codes are available at (https : //github.”
MethodPerez-Rathke, A., Sun, Q., Wang, B., Boeva, V., Shao, Z., & Liang, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/854190 · Cited by 1
Novel imprints in mouse blastocysts are predominantly DNA methylation independentPreprint
Santini, L., Halbritter, F., Titz‐Teixeira, F., Suzuki, T., Asami, M., Ramesmayer, J., Ma, X., Lackner, A., Warr, N., Pauler, F. M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.03.366948 · Cited by 1
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Robust 3D Modelling Reveals Spatiosyntenic Properties of Animal GenomesPreprint
Clarence, T., Robert, N. S. M., Sarigol, F., Fu, X., Bates, P. B., & Simakov, O. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4168315 · Cited by 1
Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid PigsPreprint
Li, M. (2022) · Research Square · doi:10.21203/rs.3.rs-2392032/v1 · Cited by 1
Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid PigsPreprint
Lin, Y., Li, J., Gu, Y., Jin, L. G., Bai, J., Zhang, J., Wang, Y., Liu, P., Long, K., He, M., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-2392032/v2 · Cited by 1
Papale, A., & Holcman, D. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.16.520776 · Cited by 1
Scaling laws of human transcriptional activityPreprint
Hong, J., Cavga, A. D., Shah, D., Laue, E. D., & Taipale, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.10.551625 · Cited by 1
Self-citationSimultaneous single-cell chromatin architecture and gene expression sequencing by LiMCAPreprint
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Large-scale manipulation of radial positioning does not affect most aspects of genome organizationPreprint
Guetta, M., Kariti, H., Sherman, L., Israitel, L., Tel-Paz, M., Avidan, N., Shemer, R., & Kaplan, N. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.22.609170 · Cited by 1
Condensins-mediated mitotic folding persists as a structural echo in interphase chromatinPreprint
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Asymmetric centromere and gene locus positioning in Drosophila neural stem cellsPreprint
Taylor, J. A., & Cabernard, C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.14.676095 · Cited by 1
Distinctive nuclear zone for RAD51-mediated homologous recombinational DNA repairPreprint
Horikoshi, Y., Shima, H., 孫, 継., Kobayashi, W., Schmid, V. J., Ochiai, H., Shi, L., Fukuto, A., Kinugasa, Y., Kurumizaka, H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.29.470307 · Cited by 1
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Self-citationOrderly mitosis shapes interphase genome architecturePreprint
Guin, K., Keikhosravi, A., Chari, R., Pegoraro, G., & Misteli, T. (2026) · eLife · doi:10.7554/elife.108410.2 · Cited by 1
Zooming in on nuclear organization
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Transcription Factor Binding Dynamics and Spatial Co-localization In Human Genome
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Metadata
- Authors
- Stevens, T. J., Lando, D., Basu, S., Atkinson, L. P., Cao, Y., Lee, S. F., Leeb, M., Wohlfahrt, K. J., Boucher, W., O’Shaughnessy-Kirwan, A., Cramard, J., Faure, A. J., Ralser, M., Blanco, E., Morey, L., Sansó, M., Palayret, M. G. S., Lehner, B., Di Croce, L., Wutz, A., Hendrich, B., Klenerman, D., & Laue, E. D.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- European Molecular Biology Laboratory (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Laue, Ernest D.
- ORCID
- Venue
- Nature
- Published
- 2017-03-13
- Volume
- 544
- Issue
- 7648
- Pages
- 59-64
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5385134
- OpenAlex
- W2597274540
- Cited by
- 832
- References
- 41
- Citations by year
- 2026: 42 · 2025: 73 · 2024: 62 · 2023: 71 · 2022: 95 · 2021: 115 · 2020: 95 · 2019: 121 · 2018: 99 · 2017: 58
- FWCI
- 41.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (082010/Z/07/Z, 277899, 206291/Z/17/Z, 082010)
- Medical Research Council (MR/M010082/1, MC_PC_12009, MR/P019471/1)
- Cancer Research UK Cambridge Institute, University of Cambridge
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- 3D genome organization, single-cell Hi-C, chromosome conformation capture, topologically associating domains, chromatin looping, lamina-associated domains, mouse embryonic stem cells, cell-to-cell variability, pluripotency factors, nucleosome remodeling, nuclear organization
- MeSH terms
- Mouse Embryonic Stem Cells, CCCTC-Binding Factor, Cohesins, Animals, Chromosomal Proteins, Non-Histone, DNA, Enhancer Elements, Genetic, Gene Expression Regulation, Haploidy, Models, Molecular, Molecular Conformation, Nucleosomes, Promoter Regions, Genetic, Repressor Proteins, Reproducibility of Results, G1 Phase, Genome, Cell Cycle Proteins, Chromosomes, Mammalian, Chromatin Assembly and Disassembly, Mice, Gene Regulatory Networks, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Molecular Imaging, Single-Cell Analysis
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