Justification of quasi-stationary approximation in models of gene expression of a self-regulating protein

TL;DR

This paper analyzes a gene regulation model with multiple time scales, demonstrating how quasi-stationary approximations simplify the model while preserving key dynamics, and explores stability and differences in model behavior.

Contribution

It introduces a multi-scale analysis of Hes1 gene regulation, deriving simplified models using the Tikhonov theorem based on process time scale separation.

Findings

Quasi-stationary approximation is valid under certain time scale assumptions.

Different models emerge depending on the relation between binding and dimer formation time scales.

Numerical experiments reveal differences in dynamics between the full and reduced models.

Abstract

We analyse a model of Hes1 gene transcription and protein synthesis with a negative feedback loop. The effect of multiple binding sites in the Hes1 promoter as well as the dimer formation process are taken into account. We consider three, possibly different, time scales connected with: (i) the process of binding to/dissolving from a binding site, (ii) formation and dissociation of dimers, (iii) production and degradation of Hes1 protein and its mRNA. Assuming that the first two processes are much faster than the third one, using the Tikhonov theorem, we reduce in two steps the full model to the classical Hes1 model. In the intermediate step two different models are derived depending on the relation between the time scales of processes (i) and (ii). The asymptotic behaviour of the solutions of systems are studied. We investigate the stability of the positive steady state and perform some numerical experiments showing differences in dynamics of the considered models.