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Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding
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 compa...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279381/ https://www.ncbi.nlm.nih.gov/pubmed/35831310 http://dx.doi.org/10.1038/s41467-022-31856-6 |
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author | Conte, Mattia Irani, Ehsan Chiariello, Andrea M. Abraham, Alex Bianco, Simona Esposito, Andrea Nicodemi, Mario |
author_facet | Conte, Mattia Irani, Ehsan Chiariello, Andrea M. Abraham, Alex Bianco, Simona Esposito, Andrea Nicodemi, Mario |
author_sort | Conte, Mattia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9279381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92793812022-07-15 Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding Conte, Mattia Irani, Ehsan Chiariello, Andrea M. Abraham, Alex Bianco, Simona Esposito, Andrea Nicodemi, Mario Nat Commun Article 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. Nature Publishing Group UK 2022-07-13 /pmc/articles/PMC9279381/ /pubmed/35831310 http://dx.doi.org/10.1038/s41467-022-31856-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Conte, Mattia Irani, Ehsan Chiariello, Andrea M. Abraham, Alex Bianco, Simona Esposito, Andrea Nicodemi, Mario Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title | Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title_full | Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title_fullStr | Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title_full_unstemmed | Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title_short | Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
title_sort | loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279381/ https://www.ncbi.nlm.nih.gov/pubmed/35831310 http://dx.doi.org/10.1038/s41467-022-31856-6 |
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