Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
Abstract 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 nucleosom...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39907-2 |
| _version_ | 1797778853880397824 |
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| author | Sangram Kadam Kiran Kumari Vinoth Manivannan Shuvadip Dutta Mithun K. Mitra Ranjith Padinhateeri |
| author_facet | Sangram Kadam Kiran Kumari Vinoth Manivannan Shuvadip Dutta Mithun K. Mitra Ranjith Padinhateeri |
| author_sort | Sangram Kadam |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T23:22:33Z |
| format | Article |
| id | doaj.art-b0bbf13063214f7e8c39c964867eba33 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T23:22:33Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b0bbf13063214f7e8c39c964867eba332023-07-16T11:21:17ZengNature PortfolioNature Communications2041-17232023-07-0114111410.1038/s41467-023-39907-2Predicting scale-dependent chromatin polymer properties from systematic coarse-grainingSangram Kadam0Kiran Kumari1Vinoth Manivannan2Shuvadip Dutta3Mithun K. Mitra4Ranjith Padinhateeri5Department of Biosciences and Bioengineering, Indian Institute of Technology BombayDepartment of Biosciences and Bioengineering, Indian Institute of Technology BombayDepartment of Biosciences and Bioengineering, Indian Institute of Technology BombayDepartment of Physics, Indian Institute of Technology BombayDepartment of Physics, Indian Institute of Technology BombayDepartment of Biosciences and Bioengineering, Indian Institute of Technology BombayAbstract 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.https://doi.org/10.1038/s41467-023-39907-2 |
| spellingShingle | Sangram Kadam Kiran Kumari Vinoth Manivannan Shuvadip Dutta Mithun K. Mitra Ranjith Padinhateeri Predicting scale-dependent chromatin polymer properties from systematic coarse-graining Nature Communications |
| 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 |
| url | https://doi.org/10.1038/s41467-023-39907-2 |
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