Regulation of gene expression in bacteria results from the interplay between hundreds of transcriptional factors (TFs) at target promoters. However, how the arrangement of binding sites for TFs generates the regulatory logic of promoters is not well-known. Here, we generated and fully characterized a library of synthetic complex promoters for the global regulators, CRP and IHF, in Escherichia coli, which are formed by a weak −35/–10 consensus sequence preceded by four combinatorial binding sites for these two TFs. Using this approach, we found that while cis-elements for CRP preferentially activate promoters when located immediately upstream of the promoter consensus, binding sites for IHF mainly function as “UP” elements and stimulate transcription in several different architectures in the absence of this protein. However, the combination of CRP- and IHF-binding sites resulted in emergent properties in these complex promoters, where the activity of combinatorial promoters cannot be predicted from the individual behavior of its components. Taken together, the results presented here add to the information on architecture-logic of complex promoters in bacteria.

中文翻译：

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复杂的合成细菌启动子的新兴特性

细菌中基因表达的调节是由靶启动子上数百个转录因子（TFs）之间的相互作用引起的。然而，TF的结合位点的排列如何产生启动子的调节逻辑尚不为人所知。在这里，我们为大肠杆菌中的全球调节子CRP和IHF生成了合成复合物启动子并对其进行了充分表征，所述启动子由弱的-35 / -10共有序列形成，后接这两个TF的四个组合结合位点。使用这种方法，我们发现，尽管顺当位于启动子共有序列的上游时，CRP的C-元素优先激活启动子，IHF的结合位点主要起“ UP”元件的作用，并在缺少该蛋白的情况下以几种不同的结构刺激转录。但是，CRP和IHF结合位点的组合在这些复杂的启动子中产生了新兴的特性，其中组合启动子的活性无法从其组分的单独行为来预测。综上所述，此处介绍的结果将增加细菌中复杂启动子的结构逻辑信息。