Order and stochasticity in the folding of individual Drosophila genomes

Sergey V. Ulianov, Vlada V. Zakharova, Aleksandra A. Galitsyna, Pavel I. Kos, Kirill E. Polovnikov, Ilya M. Flyamer, Elena A. Mikhaleva, Ekaterina E. Khrameeva, Diego Germini, Mariya D. Logacheva, Alexey A. Gavrilov, Alexander S. Gorsky, Sergey K. Nechaev, Mikhail S. Gelfand, Yegor S. Vassetzky, Alexander V. Chertovich, Yuri Y. Shevelyov and Sergey V. Razin ()
Additional contact information
Sergey V. Ulianov: Russian Academy of Sciences
Vlada V. Zakharova: Russian Academy of Sciences
Aleksandra A. Galitsyna: Skolkovo Institute of Science and Technology
Pavel I. Kos: M.V. Lomonosov Moscow State University
Kirill E. Polovnikov: Skolkovo Institute of Science and Technology
Ilya M. Flyamer: University of Edinburgh
Elena A. Mikhaleva: National Research Centre “Kurchatov Institute”
Ekaterina E. Khrameeva: Skolkovo Institute of Science and Technology
Diego Germini: Université Paris-Sud Paris-Saclay, Institut Gustave Roussy
Mariya D. Logacheva: Skolkovo Institute of Science and Technology
Alexey A. Gavrilov: Russian Academy of Sciences
Alexander S. Gorsky: Russian Academy of Sciences
Sergey K. Nechaev: Interdisciplinary Scientific Center Poncelet (CNRS UMI 2615)
Mikhail S. Gelfand: Skolkovo Institute of Science and Technology
Yegor S. Vassetzky: Université Paris-Sud Paris-Saclay, Institut Gustave Roussy
Alexander V. Chertovich: M.V. Lomonosov Moscow State University
Yuri Y. Shevelyov: National Research Centre “Kurchatov Institute”
Sergey V. Razin: Russian Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20292-z

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