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

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