Quantifying epigenetic stability with minimum action paths.

Physical Review. E
Amogh Sood, Bin Zhang

Abstract

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 epi...Continue Reading

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Citations

Sep 29, 2020·PLoS Computational Biology·Wen Jun XieBin Zhang
Nov 21, 2020·Physical Review. E·Bhaswati BhattacharyyaMasaki Sasai
Jul 10, 2021·The Journal of Chemical Physics·Xingcheng LinBin Zhang

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