Cell-type switches induced by stochastic histone modification inheritance

Abstract

Cell plasticity is important for tissue developments during which somatic cells may switch between distinct states. Genetic networks to yield multistability are usually required to yield multiple states, and either external stimuli or noise in gene expressions are trigger signals to induce cell-type switches. In many biological systems, cells show highly plasticity and can switch between different states spontaneously, but maintaining the dynamic equilibrium of the cell population. Here, we considered a mechanism of spontaneous cell-type switches through the combination between gene regulation network and stochastic epigenetic state transitions. We presented a mathematical model that consists of a standard positive feedback loop with changes of histone modifications during cell cycling. Based on the model, nucleosome state of an associated gene is a random process during cell cycling, and hence introduces an inherent noise to gene expression, which can automatically induce cell-type switches in cell cycling. Our model reveals a simple mechanism of spontaneous cell-type switches through a stochastic histone modification inheritance during cell cycle. This mechanism is inherent to the normal cell cycle process, and is independent to the external signals.