Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

TL;DR

This study explores how multiple binding sites for transcriptional repressors influence gene expression dynamics, revealing that they can induce regular bursting and reduce noise, thus providing insights into cellular regulation mechanisms.

Contribution

It introduces a stochastic model of negative autoregulation with multiple binding sites, demonstrating their roles in gene expression bursting and noise suppression.

Findings

Multiple binding sites induce regular gene expression bursting.

Tuning repression thresholds can suppress fluctuations.

Multiple sites can both promote regularity and reduce noise.

Abstract

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators.