Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations
Abstract Background The structure and mechanical properties of chromatin impact DNA functions and nuclear architecture but remain poorly understood. In budding yeast, a simple polymer model with minimal sequence-specific constraints and a small number of structural parameters can explain diverse exp...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Genome Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13059-017-1199-x |
| _version_ | 1819067224937201664 |
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| author | Jean-Michel Arbona Sébastien Herbert Emmanuelle Fabre Christophe Zimmer |
| author_facet | Jean-Michel Arbona Sébastien Herbert Emmanuelle Fabre Christophe Zimmer |
| author_sort | Jean-Michel Arbona |
| collection | DOAJ |
| description | Abstract Background The structure and mechanical properties of chromatin impact DNA functions and nuclear architecture but remain poorly understood. In budding yeast, a simple polymer model with minimal sequence-specific constraints and a small number of structural parameters can explain diverse experimental data on nuclear architecture. However, how assumed chromatin properties affect model predictions was not previously systematically investigated. Results We used hundreds of dynamic chromosome simulations and Bayesian inference to determine chromatin properties consistent with an extensive dataset that includes hundreds of measurements from imaging in fixed and live cells and two Hi-C studies. We place new constraints on average chromatin fiber properties, narrowing down the chromatin compaction to ~53–65 bp/nm and persistence length to ~52–85 nm. These constraints argue against a 20–30 nm fiber as the exclusive chromatin structure in the genome. Our best model provides a much better match to experimental measurements of nuclear architecture and also recapitulates chromatin dynamics measured on multiple loci over long timescales. Conclusion This work substantially improves our understanding of yeast chromatin mechanics and chromosome architecture and provides a new analytic framework to infer chromosome properties in other organisms. |
| first_indexed | 2024-12-21T16:14:52Z |
| format | Article |
| id | doaj.art-f7357732354b4a909d56de214e3bb49f |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-21T16:14:52Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-f7357732354b4a909d56de214e3bb49f2022-12-21T18:57:43ZengBMCGenome Biology1474-760X2017-05-0118111510.1186/s13059-017-1199-xInferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulationsJean-Michel Arbona0Sébastien Herbert1Emmanuelle Fabre2Christophe Zimmer3Unité Imagerie et Modélisation, Institut PasteurUnité Imagerie et Modélisation, Institut PasteurChromosome Biology and Dynamics, Hôpital Saint LouisUnité Imagerie et Modélisation, Institut PasteurAbstract Background The structure and mechanical properties of chromatin impact DNA functions and nuclear architecture but remain poorly understood. In budding yeast, a simple polymer model with minimal sequence-specific constraints and a small number of structural parameters can explain diverse experimental data on nuclear architecture. However, how assumed chromatin properties affect model predictions was not previously systematically investigated. Results We used hundreds of dynamic chromosome simulations and Bayesian inference to determine chromatin properties consistent with an extensive dataset that includes hundreds of measurements from imaging in fixed and live cells and two Hi-C studies. We place new constraints on average chromatin fiber properties, narrowing down the chromatin compaction to ~53–65 bp/nm and persistence length to ~52–85 nm. These constraints argue against a 20–30 nm fiber as the exclusive chromatin structure in the genome. Our best model provides a much better match to experimental measurements of nuclear architecture and also recapitulates chromatin dynamics measured on multiple loci over long timescales. Conclusion This work substantially improves our understanding of yeast chromatin mechanics and chromosome architecture and provides a new analytic framework to infer chromosome properties in other organisms.http://link.springer.com/article/10.1186/s13059-017-1199-xChromatinChromosomesNuclear architecturePolymer modelsYeast |
| spellingShingle | Jean-Michel Arbona Sébastien Herbert Emmanuelle Fabre Christophe Zimmer Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations Genome Biology Chromatin Chromosomes Nuclear architecture Polymer models Yeast |
| title | Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations |
| title_full | Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations |
| title_fullStr | Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations |
| title_full_unstemmed | Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations |
| title_short | Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations |
| title_sort | inferring the physical properties of yeast chromatin through bayesian analysis of whole nucleus simulations |
| topic | Chromatin Chromosomes Nuclear architecture Polymer models Yeast |
| url | http://link.springer.com/article/10.1186/s13059-017-1199-x |
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