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Cited by 64Genomics and Chromatin DynamicsChromosomal and Genetic VariationsNuclear Structure and Function

Order and stochasticity in the folding of individual Drosophila genomes

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Ulianov, Sergey V., Zakharova, Vlada V., Galitsyna, Aleksandra A., Kos, Pavel I., Polovnikov, Kirill E., Flyamer, Ilya M., Mikhaleva, Elena A., Khrameeva, Ekaterina E. +10 more·2021·Nature Communications
DOI 10.1038/s41467-020-20292-zPMC PMC7782554
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Abstract

Mammalian and Drosophila genomes are partitioned into topologically associating domains (TADs). Although this partitioning has been reported to be functionally relevant, it is unclear whether TADs represent true physical units located at the same genomic positions in each cell nucleus or emerge as an average of numerous alternative chromatin folding patterns in a cell population. Here, we use a single-nucleus Hi-C technique to construct high-resolution Hi-C maps in individual Drosophila genomes. These maps demonstrate chromatin compartmentalization at the megabase scale and partitioning of the genome into non-hierarchical TADs at the scale of 100 kb, which closely resembles the TAD profile in the bulk in situ Hi-C data. Over 40% of TAD boundaries are conserved between individual nuclei and possess a high level of active epigenetic marks. Polymer simulations demonstrate that chromatin folding is best described by the random walk model within TADs and is most suitably approximated by a crumpled globule build of Gaussian blobs at longer distances. We observe prominent cell-to-cell variability in the long-range contacts between either active genome loci or between Polycomb-bound regions, suggesting an important contribution of stochastic processes to the formation of the Drosophila 3D genome.

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  • The best single-cell Hi-C map resolution reported so far is 10 Kb.

    “The best single-cell Hi-C map resolution reported so far is 10 Kb [143].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [143]

    The Results section reports single-nucleus Hi-C maps at up to 10-kb resolution. The paper does not establish that 10 kb was the best resolution reported across all single-cell Hi-C studies; its Methods also say the data were binned at 1 kb. No page number is available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Only a portion of TAD borders are shared between most individual cells, whereas other borders appear to be variable.

    “It was also found that only a portion of TAD borders are shared between most individual cells, whereas other borders appear to be variable [142,143].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [143]

  • Single-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 [143]

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Authors
Ulianov, S. V., Zakharova, V. V., Galitsyna, A. A., Kos, P. I., Polovnikov, K. E., Flyamer, I. M., Mikhaleva, E. A., Khrameeva, E. E., Germini, D., Logacheva, M. D., Gavrilov, A. A., Gorsky, A. S., Nechaev, S. K., Gelfand, M. S., Vassetzky, Y. S., Chertovich, A. V., Shevelyov, Y. Y., & Razin, S. V.
Affiliations
  • Russian Academy of Sciences (RU)
  • Université Paris-Sud (FR)
  • Skolkovo Institute of Science and Technology (RU)
  • Lomonosov Moscow State University (RU)
  • Institute of Genetics and Cancer (GB)
  • Kurchatov Institute (RU)
Corresponding author
Razin, Sergey V.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-01-04
Volume
12
Issue
1
Pages
41-41
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-20292-z
PMC
PMC7782554
OpenAlex
W3120518704
Cited by
64
References
19
Citations by year
2026: 4 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 18 · 2021: 11
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Russian Science Foundation (19-14-00016, 19-74-00112)
  • Russian Foundation for Basic Research (18-29-13013, 19-34-90136, 18-29-13041)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
topologically associating domains, 3D genome organization, chromatin folding, Drosophila genome, cell-to-cell variability, random walks, long-range chromatin contacts, epigenetic modifications, polymer simulation
MeSH terms
Animals, Biopolymers, Chromatin, Drosophila melanogaster, Haploidy, Models, Genetic, Nucleic Acid Conformation, Stochastic Processes, X Chromosome, Databases, Genetic, Epigenesis, Genetic, Genome, Insect

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