美国能源部联合基因组研究所 Ronan C. O’Malley 团队取得了一项新突破。他们发现了细菌基因组调控的持续性和可塑性。相关论文于2021年11月25日在线发表在《自然—方法学》杂志上。

研究人员报告了一种高通量方法，用于表征跨物种的转录因子(transcription factor, TF ) 与靶基因相互作用，并将其应用于 48 种细菌的 354 个 TF上，生成了 17,000 个基因组范围内的结合图谱。该数据集揭示了转录调节模块具有保守性以及快速进化的特征。他们观察到一些 TF 维持了原来的转录和识别功能，而靶标位点的排列和识别特征却发生了变化，在某些情况下编码全新的功能。研究人员进一步整合了表型信息来定义新的功能调节模块和途径。

最后，他们在基因组DNA上鉴定出了 242 个新的 TF 结合基序，包括增加了 70% 的已知大肠杆菌（Escherichia coli）结合基序，并且在假单胞菌（Pseudomonas simiae）中发现了第一个注释，从而揭示了细菌启动子结构的高度保守性。他们的方法为原核生物和真核生物中遗传途径的功能表征提供了一种通用的工具。

据了解，生物通过转录因子(TF)与其靶基因的相互作用来调控细胞功能，尽管在大多数物种中这些调节关系在很大程度上是未知的。

附：英文原文

Title: Persistence and plasticity in bacterial gene regulation

Author: Baumgart, Leo A., Lee, Ji Eun, Salamov, Asaf, Dilworth, David J., Na, Hyunsoo, Mingay, Matthew, Blow, Matthew J., Zhang, Yu, Yoshinaga, Yuko, Daum, Chris G., OMalley, Ronan C.

Issue&Volume: 2021-11-25

Abstract: Organisms orchestrate cellular functions through transcription factor (TF) interactions with their target genes, although these regulatory relationships are largely unknown in most species. Here we report a high-throughput approach for characterizing TF–target gene interactions across species and its application to 354 TFs across 48 bacteria, generating 17,000 genome-wide binding maps. This dataset revealed themes of ancient conservation and rapid evolution of regulatory modules. We observed rewiring, where the TF sensing and regulatory role is maintained while the arrangement and identity of target genes diverges, in some cases encoding entirely new functions. We further integrated phenotypic information to define new functional regulatory modules and pathways. Finally, we identified 242 new TF DNA binding motifs, including a 70% increase of known Escherichia coli motifs and the first annotation in Pseudomonas simiae, revealing deep conservation in bacterial promoter architecture. Our method provides a versatile tool for functional characterization of genetic pathways in prokaryotes and eukaryotes.

DOI: 10.1038/s41592-021-01312-2

Source: https://www.nature.com/articles/s41592-021-01312-2