title: Noise can induce bimodality in positive transcriptional feedback loops without bistability.
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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Tsz-Leung
authors.initials: TL
authors.lastname: To
authors.forename: Narendra
authors.initials: N
authors.lastname: Maheshri
mesh_terms: D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004318:Doxycycline / Q000378:metabolism; D025461:Feedback, Physiological; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D015233:Models, Statistical; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004318:Doxycycline