Model reduction and stochastic analysis of the histone modification circuit
2022 European Control Conference (ECC), London, United Kingdom, 2022
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
IEEE
2024
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| Online Access: | https://hdl.handle.net/1721.1/155700 |
| _version_ | 1826195206595149824 |
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| author | Bruno, Simone Williams, Ruth J. Del Vecchio, Domitilla |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Bruno, Simone Williams, Ruth J. Del Vecchio, Domitilla |
| author_sort | Bruno, Simone |
| collection | MIT |
| description | 2022 European Control Conference (ECC), London, United Kingdom, 2022 |
| first_indexed | 2024-09-23T10:09:25Z |
| format | Article |
| id | mit-1721.1/155700 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:18:57Z |
| publishDate | 2024 |
| publisher | IEEE |
| record_format | dspace |
| spelling | mit-1721.1/1557002024-12-23T05:10:29Z Model reduction and stochastic analysis of the histone modification circuit Bruno, Simone Williams, Ruth J. Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering 2022 European Control Conference (ECC), London, United Kingdom, 2022 Epigenetic cell memory (ECM), the inher-itance of gene expression patterns without changes in genetic sequence, is a critical property of multi-cellular organisms. Chromatin state, as dictated by histone covalent modifications, has recently appeared as a mediator of ECM. In this paper, we conduct a stochastic analysis of the histone modification circuit that controls chromatin state to determine key biological parameters that affect ECM. Specifically, we derive a one-dimensional Markov chain model of the circuit and analytically evaluate both the stationary probability distribution of chromatin state and the mean time to switch between active and repressed chromatin states. We then validate our analytical findings using stochastic simulations of the original higher dimensional circuit reaction model. Our analysis shows that as the speed of basal decay of histone modifications decreases compared to the speed of autocatalysis, the stationary probability distribution becomes bimodal and increasingly concentrated about the active and repressed chromatin states. Accordingly, the switching time between active and repressed chromatin states becomes larger. These results indicate that time scale separation among key constituent processes of the histone modification circuit controls ECM. 2024-07-17T20:56:53Z 2024-07-17T20:56:53Z 2022-07-12 2024-07-17T20:51:55Z Article http://purl.org/eprint/type/ConferencePaper https://hdl.handle.net/1721.1/155700 S. Bruno, R. J. Williams and D. Del Vecchio, "Model reduction and stochastic analysis of the histone modification circuit," 2022 European Control Conference (ECC), London, United Kingdom, 2022, pp. 264-271. en 10.23919/ecc55457.2022.9838047 2022 European Control Conference (ECC) Creative Commons Attribution-Noncommercial-ShareAlike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf IEEE Author |
| spellingShingle | Bruno, Simone Williams, Ruth J. Del Vecchio, Domitilla Model reduction and stochastic analysis of the histone modification circuit |
| title | Model reduction and stochastic analysis of the histone modification circuit |
| title_full | Model reduction and stochastic analysis of the histone modification circuit |
| title_fullStr | Model reduction and stochastic analysis of the histone modification circuit |
| title_full_unstemmed | Model reduction and stochastic analysis of the histone modification circuit |
| title_short | Model reduction and stochastic analysis of the histone modification circuit |
| title_sort | model reduction and stochastic analysis of the histone modification circuit |
| url | https://hdl.handle.net/1721.1/155700 |
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