Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories
Chromatin moves with subdiffusive and spatially constrained dynamics within the cell nucleus. Here, we use single-locus tracking by time-lapse fluorescence microscopy to uncover information regarding the forces that influence chromatin movement following the induction of a persistent DNA double-stra...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
2211-1247
2017
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| Online Access: | http://hdl.handle.net/1721.1/109829 https://orcid.org/0000-0002-8594-6529 |
| _version_ | 1811077381741346816 |
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| author | Amitai, Assaf Seeber, Andrew Gasser, Susan M. Holcman, David |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Amitai, Assaf Seeber, Andrew Gasser, Susan M. Holcman, David |
| author_sort | Amitai, Assaf |
| collection | MIT |
| description | Chromatin moves with subdiffusive and spatially constrained dynamics within the cell nucleus. Here, we use single-locus tracking by time-lapse fluorescence microscopy to uncover information regarding the forces that influence chromatin movement following the induction of a persistent DNA double-strand break (DSB). Using improved time-lapse imaging regimens, we monitor trajectories of tagged DNA loci at a high temporal resolution, which allows us to extract biophysical parameters through robust statistical analysis. Polymer modeling based on these parameters predicts chromatin domain expansion near a DSB and damage extrusion from the domain. Both phenomena are confirmed by live imaging in budding yeast. Calculation of the anomalous exponent of locus movement allows us to differentiate forces imposed on the nucleus through the actin cytoskeleton from those that arise from INO80 remodeler-dependent changes in nucleosome organization. Our analytical approach can be applied to high-density single-locus trajectories obtained in any cell type. |
| first_indexed | 2024-09-23T10:42:07Z |
| format | Article |
| id | mit-1721.1/109829 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:42:07Z |
| publishDate | 2017 |
| publisher | 2211-1247 |
| record_format | dspace |
| spelling | mit-1721.1/1098292022-09-30T22:24:13Z Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories Amitai, Assaf Seeber, Andrew Gasser, Susan M. Holcman, David Massachusetts Institute of Technology. Institute for Medical Engineering & Science Amitai, Assaf Chromatin moves with subdiffusive and spatially constrained dynamics within the cell nucleus. Here, we use single-locus tracking by time-lapse fluorescence microscopy to uncover information regarding the forces that influence chromatin movement following the induction of a persistent DNA double-strand break (DSB). Using improved time-lapse imaging regimens, we monitor trajectories of tagged DNA loci at a high temporal resolution, which allows us to extract biophysical parameters through robust statistical analysis. Polymer modeling based on these parameters predicts chromatin domain expansion near a DSB and damage extrusion from the domain. Both phenomena are confirmed by live imaging in budding yeast. Calculation of the anomalous exponent of locus movement allows us to differentiate forces imposed on the nucleus through the actin cytoskeleton from those that arise from INO80 remodeler-dependent changes in nucleosome organization. Our analytical approach can be applied to high-density single-locus trajectories obtained in any cell type. 2017-06-13T18:18:01Z 2017-06-13T18:18:01Z 2017-01 2016-12 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/109829 Amitai, Assaf; Seeber, Andrew; Gasser, Susan M. and Holcman, David. “Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories.” Cell Reports 18, no. 5 (January 2017): 1200–1214 © 2017 The Author(s) https://orcid.org/0000-0002-8594-6529 en_US http://dx.doi.org/10.1016/j.celrep.2017.01.018 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf 2211-1247 Elsevier |
| spellingShingle | Amitai, Assaf Seeber, Andrew Gasser, Susan M. Holcman, David Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title | Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title_full | Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title_fullStr | Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title_full_unstemmed | Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title_short | Visualization of Chromatin Decompaction and Break Site Extrusion as Predicted by Statistical Polymer Modeling of Single-Locus Trajectories |
| title_sort | visualization of chromatin decompaction and break site extrusion as predicted by statistical polymer modeling of single locus trajectories |
| url | http://hdl.handle.net/1721.1/109829 https://orcid.org/0000-0002-8594-6529 |
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