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Noise Can Induce Bimodality in Positive Transcriptional Feedback Loops Without Bistability

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Science  26 Feb 2010:
Vol. 327, Issue 5969, pp. 1142-1145
DOI: 10.1126/science.1178962

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Abstract

Transcriptional positive-feedback loops are widely associated with bistability, characterized by two stable expression states that allow cells to respond to analog signals in a digital manner. Using a synthetic system in budding yeast, we show that positive feedback involving a promoter with multiple transcription factor (TF) binding sites can induce a steady-state bimodal response without cooperative binding of the TF. Deterministic models of this system do not predict bistability. Rather, the bimodal response requires a short-lived TF and stochastic fluctuations in the TF’s expression. Multiple binding sites provide these fluctuations. Because many promoters possess multiple binding sites and many TFs are unstable, positive-feedback loops in gene regulatory networks may exhibit bimodal responses, but not necessarily because of deterministic bistability, as is commonly thought.

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