Absolute Rate Theories of Epigenetic Stability

Abstract

Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of the rare cellular states that allow epigenetic escape, and the transmission factor, depend on the rates of DNA binding and unbinding events and on the rates of protein synthesis and degradation. Different mechanisms of escape from the stable attractors occur in the nonadiabatic, weakly adiabatic and strictly adiabatic regimes, characterized by the relative values of those input rates.

8 pages, 3 figures

References in corpus (5)

• Sampling rare switching events in biochemical networks
• Stochastic gene expression as a many body problem
• Structure of Stochastic Dynamics near Fixed Points
• Self consistent proteomic field theory of stochastic gene switches
• Optimal Path to Epigenetic Switching

Cited by in corpus (38)

• Nonequilibrium Physics in Biology
• Stochastic phenotype transition of a single cell in an intermediate region of gene-state switching
• Extrinsic noise driven phenotype switching in a self-regulating gene
• Deterministic characterization of stochastic genetic circuits
• Stability and multi-attractor dynamics of a toggle switch based on a two-stage model of stochastic gene expression
• Stochastic timing in gene expression for simple regulatory strategies
• Quantitative Immunology for Physicists
• A stochastic spectral analysis of transcriptional regulatory cascades
• Exponential sensitivity of noise-driven switching in genetic networks
• DNA looping provides stability and robustness to the bacteriophage lambda switch
• Bistable switching asymptotics for the self regulating gene
• Reaction coordinates for the flipping of genetic switches
• A framework towards understanding mesoscopic phenomena: Emergent unpredictability, symmetry breaking and dynamics across scales
• A stochastic and dynamical view of pluripotency in mouse embryonic stem cells
• Relaxation rates of gene expression kinetics reveal the feedback signs of autoregulatory gene networks
• The Influence of Decoys on the Noise and Dynamics of Gene Expression
• Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch
• Metastable behavior in Markov processes with internal states
• Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics
• What makes the lac-pathway switch: identifying the fluctuations that trigger phenotype switching in gene regulatory systems
• Dichotomous noise models of gene switches
• Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators
• Effects of the DNA state fluctuation on single-cell dynamics of self-regulating gene
• Quantitative Analysis of a Transient Dynamics of a Gene Regulatory Network
• Stochastic epigenetic dynamics of gene switching
• Testing the transition state theory in stochastic dynamics of a genetic switch
• Extending the dynamic range of transcription factor action by translational regulation
• Mean-field vs. stochastic models for transcriptional regulation
• Irreversibility in Bacterial Regulatory Networks
• Resonant activation: a strategy against bacterial persistence
• Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions
• Markov State Models of Gene Regulatory Networks
• Dissipation in non-steady state regulatory circuits
• A new mechanism of development and differentiation through slow binding/unbinding of regulatory proteins to the genes
• Switching off: the phenotypic transition to the uninduced state of the lactose uptake pathway
• Reconstructing an epigenetic landscape using a genetic `pulling' approach
• Topology of the simplest gene switch
• Global View of Bionetwork Dynamics: Adaptive Landscape