Quantifying epigenetic stability with minimum action paths
Name
PhysRevE.101.062409.pdf
Description
Published version
Size
563.51 KB
Format
Adobe PDF
Checksum (MD5)
3eb6170bb9a55c165da48c6c1033a1e9
Author(s)
Sood, Amogh
Zhang, Bin
Date Issued
2020
Journal
Physical Review E
Publisher
American Physical Society (APS)
Version
Final published version
Abstract
© 2020 American Physical Society. Chromatin can adopt multiple stable, heritable states with distinct histone modifications and varying levels of gene expression. Insight on the stability and maintenance of such epigenetic states can be gained by mathematical modeling of stochastic reaction networks for histone modifications. Analytical results for the kinetic networks are particularly valuable. Compared to computationally demanding numerical simulations, they often are more convenient at evaluating the robustness of conclusions with respect to model parameters. In this communication, we developed a second-quantization-based approach that can be used to analyze discrete stochastic models with a fixed, finite number of particles using a representation of the SU(2) algebra. We applied the approach to a kinetic model of chromatin states that captures the feedback between nucleosomes and the enzymes conferring histone modifications. Using a path-integral expression for the transition probability, we computed the epigenetic landscape that helps to identify the emergence of bistability and the most probable path connecting the two steady states. We anticipate the generalizability of the approach will make it useful for studying more complicated models that couple epigenetic modifications with transcription factors and chromatin structure.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1103/PhysRevE.101.062409
