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Predicting scale-dependent chromatin polymer properties from systematic coarse-graining

Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, and the nature of inter-bead potentials are unknown. Using nucleosome-resolut...

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Autores principales: Kadam, Sangram, Kumari, Kiran, Manivannan, Vinoth, Dutta, Shuvadip, Mitra, Mithun K., Padinhateeri, Ranjith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336007/
https://www.ncbi.nlm.nih.gov/pubmed/37433821
http://dx.doi.org/10.1038/s41467-023-39907-2
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author Kadam, Sangram
Kumari, Kiran
Manivannan, Vinoth
Dutta, Shuvadip
Mitra, Mithun K.
Padinhateeri, Ranjith
author_facet Kadam, Sangram
Kumari, Kiran
Manivannan, Vinoth
Dutta, Shuvadip
Mitra, Mithun K.
Padinhateeri, Ranjith
author_sort Kadam, Sangram
collection PubMed
description Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, and the nature of inter-bead potentials are unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain chromatin and predict quantities essential for polymer representation of chromatin. We compute size distributions of chromatin beads for different coarse-graining scales, quantify fluctuations and distributions of bond lengths between neighboring regions, and derive effective spring constant values. Unlike the prevalent notion, our findings argue that coarse-grained chromatin beads must be considered as soft particles that can overlap, and we derive an effective inter-bead soft potential and quantify an overlap parameter. We also compute angle distributions giving insights into intrinsic folding and local bendability of chromatin. While the nucleosome-linker DNA bond angle naturally emerges from our work, we show two populations of local structural states. The bead sizes, bond lengths, and bond angles show different mean behavior at Topologically Associating Domain (TAD) boundaries and TAD interiors. We integrate our findings into a coarse-grained polymer model and provide quantitative estimates of all model parameters, which can serve as a foundational basis for all future coarse-grained chromatin simulations.
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spelling pubmed-103360072023-07-13 Predicting scale-dependent chromatin polymer properties from systematic coarse-graining Kadam, Sangram Kumari, Kiran Manivannan, Vinoth Dutta, Shuvadip Mitra, Mithun K. Padinhateeri, Ranjith Nat Commun Article Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, and the nature of inter-bead potentials are unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain chromatin and predict quantities essential for polymer representation of chromatin. We compute size distributions of chromatin beads for different coarse-graining scales, quantify fluctuations and distributions of bond lengths between neighboring regions, and derive effective spring constant values. Unlike the prevalent notion, our findings argue that coarse-grained chromatin beads must be considered as soft particles that can overlap, and we derive an effective inter-bead soft potential and quantify an overlap parameter. We also compute angle distributions giving insights into intrinsic folding and local bendability of chromatin. While the nucleosome-linker DNA bond angle naturally emerges from our work, we show two populations of local structural states. The bead sizes, bond lengths, and bond angles show different mean behavior at Topologically Associating Domain (TAD) boundaries and TAD interiors. We integrate our findings into a coarse-grained polymer model and provide quantitative estimates of all model parameters, which can serve as a foundational basis for all future coarse-grained chromatin simulations. Nature Publishing Group UK 2023-07-11 /pmc/articles/PMC10336007/ /pubmed/37433821 http://dx.doi.org/10.1038/s41467-023-39907-2 Text en © The Author(s) 2023 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
Kadam, Sangram
Kumari, Kiran
Manivannan, Vinoth
Dutta, Shuvadip
Mitra, Mithun K.
Padinhateeri, Ranjith
Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title_full Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title_fullStr Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title_full_unstemmed Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title_short Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
title_sort predicting scale-dependent chromatin polymer properties from systematic coarse-graining
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336007/
https://www.ncbi.nlm.nih.gov/pubmed/37433821
http://dx.doi.org/10.1038/s41467-023-39907-2
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