Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes
Open accessAbstract
Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.
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Early polymer models suggested that a single stable loop induces frequent contacts near the base or anchor of the loop, but infrequent contacts between loci inside the loop, to an extent quantitatively inconsistent with Hi-C data.
“early polymer models suggested that a single stable loop induces frequent contacts near the base or anchor of the loop, but infrequent contacts between loci inside the loop, to an extent which is quantitatively inconsistent with Hi-C data.65,66”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [66]
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“Additionally, topological constraints are distinct from other topological effects such as supercoiling of the chromatin fiber [39]; supercoiling can lead to significant insulation and facilitation [39], but may be more relevant for bacterial chromosome organization [40].”
- Authors
- Benedetti, F., Dorier, J., Burnier, Y., & Stasiak, A.
- Affiliations
- SIB Swiss Institute of Bioinformatics (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Stasiak, Andrzej
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-22
- Volume
- 42
- Issue
- 5
- Pages
- 2848-2855
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3950722
- OpenAlex
- W2086575741
- Cited by
- 113
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 11 · 2018: 14 · 2017: 18 · 2016: 18 · 2015: 7 · 2014: 12
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- University of Oxford
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (138267)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- interphase chromosomes, topological domains, DNA supercoiling, chromosome conformation, chromatin organization, Brownian dynamics
- MeSH terms
- Chromatin, Chromosomes, Computer Simulation, DNA, Superhelical, Interphase, Models, Molecular
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