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- W3211636856 abstract "Abstract Loop-extrusion and phase-separation have been proposed as mechanisms that shape chromosome large-scale spatial organization. It is unclear, however, how they perform relative to each other in explaining chromatin architecture data and whether they compete or co-exist at the single-molecule level. Here, we compare models of polymer physics based on loop-extrusion and phase-separation, as well as models where both mechanisms act simultaneously in a single molecule, against multiplexed FISH data available in human loci in IMR90 and HCT116 cells. We find that the different models recapitulate bulk Hi-C and average microscopy data. Single-molecule chromatin conformations are also well captured, especially by phase-separation based models that better reflect the experimentally reported segregation in globules of the considered genomic loci and their cell-to-cell structural variability. Such a variability is consistent with two main concurrent causes: single-cell epigenetic heterogeneity and an intrinsic thermodynamic conformational degeneracy of folding. Overall, the model combining loop-extrusion and polymer phase-separation provides a very good description of the data, particularly higher-order contacts, showing that the two mechanisms can co-exist in shaping chromatin architecture in single cells." @default.
- W3211636856 created "2021-11-22" @default.
- W3211636856 creator A5027763337 @default.
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- W3211636856 date "2021-11-02" @default.
- W3211636856 modified "2023-10-18" @default.
- W3211636856 title "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding" @default.
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- W3211636856 doi "https://doi.org/10.1101/2021.11.02.466589" @default.
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