Phase separation reduces cell-to-cell variability of transcriptional bursting

Abstract

Gene expression is a stochastic and noisy process often occurring in "bursts". Experiments have shown that the compartmentalization of proteins by liquid-liquid phase separation is conducive to reducing the noise of gene expression. Therefore, an important goal is to explore the role of bursts in phase separation noise reduction processes. We propose a coupled model that includes phase separation and a two-state gene expression process. Using the timescale separation method, we obtain approximate solutions for the expectation, variance, and noise strength of the dilute phase. We find that a higher burst frequency weakens the ability of noise reduction by phase separation, but as the burst size increases, this ability first increases and then decreases. This study provides a deeper understanding of phase separation to reduce noise in the stochastic gene expression with burst kinetics.

Keywords: Liquid-liquid phase separation; Noise strength; Stochastic gene expression; Transcriptional burst.