Systems Bioengineering Program, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Carrer Dr. Aiguader 88, 08003 Barcelona, Spain.
Systems Bioengineering Program, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Carrer Dr. Aiguader 88, 08003 Barcelona, Spain.
Cell Rep. 2018 Jul 17;24(3):755-765. doi: 10.1016/j.celrep.2018.06.059.
Organisms regulate gene expression through changes in the activity of transcription factors (TFs). In yeast, the response of genes to changes in TF activity is generally assumed to be encoded in the promoter. To directly test this assumption, we chose 42 genes and, for each, replaced the promoter with a synthetic inducible promoter and measured how protein expression changes as a function of TF activity. Most genes exhibited gene-specific TF dose-response curves not due to differences in mRNA stability, translation, or protein stability. Instead, most genes have an intrinsic ability to buffer the effects of promoter activity. This can be encoded in the open reading frame and the 3' end of genes and can be implemented by both autoregulatory feedback and by titration of limiting trans regulators. We show experimentally and computationally that, when misexpression of a gene is deleterious, this buffering insulates cells from fitness defects due to misregulation.
生物体通过改变转录因子（TF）的活性来调节基因表达。在酵母中，基因对 TF 活性变化的反应通常被认为是由启动子编码的。为了直接检验这一假设，我们选择了 42 个基因，对于每个基因，我们用合成诱导启动子替换启动子，并测量了蛋白质表达如何随 TF 活性的变化而变化。大多数基因表现出基因特异性的 TF 剂量反应曲线，而不是由于 mRNA 稳定性、翻译或蛋白质稳定性的差异。相反，大多数基因具有内在的能力来缓冲启动子活性的影响。这可以在开放阅读框和基因的 3' 端编码，并且可以通过自动调节反馈和限制转调控因子的滴定来实现。我们通过实验和计算表明，当一个基因的错误表达是有害的时，这种缓冲可以使细胞免受由于调节错误而导致的适应性缺陷。
