Landscapes and nonequilibrium fluctuations of eukaryotic gene regulation

Fuente: arXiv
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Auteurs principaux: Sasai, Masaki, Bhattacharyya, Bhaswati, Fujishiro, Shin, Horiike, Yoshiaki
Format: Preprint
Publié: 2025
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author Sasai, Masaki
Bhattacharyya, Bhaswati
Fujishiro, Shin
Horiike, Yoshiaki
author_facet Sasai, Masaki
Bhattacharyya, Bhaswati
Fujishiro, Shin
Horiike, Yoshiaki
contents Understanding the interplay among processes that occur over different timescales is a challenging issue in the physics of systems regulation. In gene regulation, the timescales for changes in chromatin states can differ from those for changes in the concentration of product protein, raising questions about how to understand their coupled dynamics. In this study, we examine the effects of these different timescales on eukaryotic gene regulation using a stochastic model that describes the landscapes and probability currents of nonequilibrium fluctuations.This model shows that slow, nonadiabatic transitions of chromatin states significantly impact gene-regulation dynamics. The simulated circular flow of the probability currents indicates a maximum entropy production when the rates of chromatin-state transitions are low in the intensely nonadiabatic regime. In the mildly nonadiabatic regime, this circular flow fosters hysteresis, suggesting that changes in chromatin states precede changes in transcription activity. Furthermore, calculations using a model of a circuit involving three core genes in mouse embryonic stem cells illustrate how the timescale difference can tune fluctuations in individual genes. These findings highlight the rich effects of nonadiabatic chromatin-state transitions on gene regulation in eukaryotic cells.
format Preprint
id arxiv_https___arxiv_org_abs_2502_10067
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Landscapes and nonequilibrium fluctuations of eukaryotic gene regulation
Sasai, Masaki
Bhattacharyya, Bhaswati
Fujishiro, Shin
Horiike, Yoshiaki
Biological Physics
Molecular Networks
Understanding the interplay among processes that occur over different timescales is a challenging issue in the physics of systems regulation. In gene regulation, the timescales for changes in chromatin states can differ from those for changes in the concentration of product protein, raising questions about how to understand their coupled dynamics. In this study, we examine the effects of these different timescales on eukaryotic gene regulation using a stochastic model that describes the landscapes and probability currents of nonequilibrium fluctuations.This model shows that slow, nonadiabatic transitions of chromatin states significantly impact gene-regulation dynamics. The simulated circular flow of the probability currents indicates a maximum entropy production when the rates of chromatin-state transitions are low in the intensely nonadiabatic regime. In the mildly nonadiabatic regime, this circular flow fosters hysteresis, suggesting that changes in chromatin states precede changes in transcription activity. Furthermore, calculations using a model of a circuit involving three core genes in mouse embryonic stem cells illustrate how the timescale difference can tune fluctuations in individual genes. These findings highlight the rich effects of nonadiabatic chromatin-state transitions on gene regulation in eukaryotic cells.
title Landscapes and nonequilibrium fluctuations of eukaryotic gene regulation
topic Biological Physics
Molecular Networks
url https://arxiv.org/abs/2502.10067