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Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding

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Item Type:Article
Title:Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding
Creators Name:Conte, M. and Irani, E. and Chiariello, A.M. and Abraham, A. and Bianco, S. and Esposito, A. and Nicodemi, M.
Abstract:Loop-extrusion and phase-separation have been proposed as mechanisms that shape chromosome 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 multiplexed 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.
Keywords:Biological Physics, Chromatin Structure
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:4070
Date:13 July 2022
Official Publication:https://doi.org/10.1038/s41467-022-31856-6
PubMed:View item in PubMed

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