Our knowledge of transcriptional responses to changes in nutrient availability comes primarily from few well-studied transcription factors (TFs), often lacking an unbiased genome-wide perspective. Leveraging recent advances allowing bacterial genomic footprinting, we comprehensively mapped the genome-wide regulatory responses of Escherichia coli to exogenous leucine, methionine, alanine, and lysine. The global TF Lrp was found to individually sense three amino acids and mount three different target gene responses. Overall, 531 genes had altered RNA polymerase occupancy, and 32 TFs responded directly or indirectly to the presence of amino acids, including regulators of membrane and osmotic pressure homeostasis. About 70% of the detected TF-DNA interactions had not been reported before. We thus identified 682 previously unknown TF-binding locations, for a subset of which the involved TFs were identified by affinity purification. This comprehensive map of amino acid regulation illustrates the incompleteness of the known transcriptional regulation network, even in E. coli.

我们对营养物质可用性变化的转录反应的了解主要来自于少数经过充分研究的转录因子（TF），通常缺乏公正的全基因组视角。利用细菌基因组足迹的最新进展，我们全面绘制了大肠杆菌对外源亮氨酸、蛋氨酸、丙氨酸和赖氨酸的全基因组调控反应。发现全局 TF Lrp 可以单独感知三种氨基酸并产生三种不同的靶基因反应。总体而言，531 个基因改变了 RNA 聚合酶的占用，32 个 TF 直接或间接对氨基酸的存在做出反应，包括膜和渗透压稳态的调节因子。大约 70% 的检测到的 TF-DNA 相互作用以前从未报道过。因此，我们鉴定了 682 个以前未知的 TF 结合位点，其中的一个子集通过亲和纯化鉴定了所涉及的 TF。这张氨基酸调控的综合图谱说明了已知的转录调控网络的不完整性，即使在大肠杆菌中也是如此。