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

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.

Novel regulatory mechanism of establishment genes of conjugative plasmids

“…Our model not only shows that the regulatory logic found in our experiments is consistent with transient pulse-like expression of target genes, but more generically shows that an auto-inhibitory motif can play this role. Negative feedback loops have been associated with keeping homeostasis, to speed up response times, taming fluctuations or the emergence of oscillations (44). Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression (44), but here we show that under the appropriate conditions of high cooperativity and differential repression of targets, they can also produce pulses of expression.…”

“…Negative feedback loops have been associated with keeping homeostasis, to speed up response times, taming fluctuations or the emergence of oscillations (44). Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression (44), but here we show that under the appropriate conditions of high cooperativity and differential repression of targets, they can also produce pulses of expression. Pulses have usually been associated to more complicated regulatory motifs like feed-forward loops (45).…”

Chemical event chain model of coupled genetic oscillators

“…systems [20,[23][24][25][26][27][28][29]. Both natural and artificial genetic oscillators exhibit pronounced amplitude and phase noise [6,12,24,[30][31][32][33][34][35][36], which limits their precision when used as a clock. To achieve temporal and spatial coherence as well as high precision, cell-autonomous oscillators are typically coupled [19,37,38].…”

Stochastic Kuramoto oscillators with discrete phase states

“…Whether a phase-continuous model is a viable description depends on the system at hand. Biochemical oscillators, for instance, operate through chemical and/or genetic feedbacks between different molecule species and * djj35@cam.ac.uk are often characterized by small numbers of molecules which are subject to fluctuations [18][19][20][21][22]. Another prominent example from biology is the cell cycle, which, while going through well-defined states, can exhibit considerable period variations [23].…”