Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2010 Feb 26;327(5969):1142-5. doi: 10.1126/science.1178962.
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.
转录正反馈回路与双稳性广泛相关，其特征是存在两种稳定的表达状态，使细胞能够以数字方式对模拟信号做出响应。使用芽殖酵母中的合成系统，我们表明涉及具有多个转录因子（TF）结合位点的启动子的正反馈可以在没有 TF 协同结合的情况下诱导稳态双峰响应。该系统的确定性模型不能预测双稳性。相反，双峰响应需要 TF 的短暂表达和 TF 表达的随机波动。多个结合位点提供了这些波动。由于许多启动子具有多个结合位点，并且许多 TF 不稳定，因此基因调控网络中的正反馈回路可能表现出双峰响应，但不一定是由于通常认为的确定性双稳性。
