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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Stevens et al. reported that combination of 3C and tagged fluorescent imaging was able to detect folding of a genomic sequence <100bp in a single cell.
“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]
The Introduction reports combining imaging with single-cell Hi-C to determine genome structures in individual cells, so the method and single-cell aspects are supported. But it specifies a 100 kb scale, and the Abstract says folding was studied down to <100 kb—not <100 bp. The imaged fluorescent tags marked proteins, not a genomic sequence. (LLM, conf=0.93)
Experimental — accuracy not yet measuredSingle-cell Hi-C studies confirm the presence of TADs in individual cells but demonstrate significant variability in their shape.
“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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- 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 · 2016: 1
- 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 › Agricultural and Biological Sciences › Plant Science › 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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