Mathematical modelling of epigenetic regulatory mechanisms in gene expression

Epigenetic Regulation is the way that expression of genes is controlled by the reversible modification of DNA, modification of histones, chromatin remodeling and interaction with noncoding RNA so that cells respond to developmental and environmental cues without changing the DNA sequence.These complex networks and their dynamic functions can be understood quantitatively using math models.A comprehensive model framework, based on ordinary differential equations and stochastic techniques, is presented in this paper that models the epigenetic mechanisms that influence the regulation of the transcription.Using parameter estimation and numerical simulation of the model, the stability of regulation, interaction of feedback and the number of states for different biological conditions are explored.Dynamic analysis demonstrates the potential for epigenetic modification to activate/silence genes and how the phenotype can vary.The framework presented here provides useful insights into the regulatory forces, enhances predictive understanding of gene expression processes, and can assist in future applications such as systems biology, precision medicine, disease modelling and therapeutic strategy development.

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