An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence.
An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence.
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铜绿假单胞菌转录因子结合特异性图谱指导新毒力调节因子的预测
作者：
Wang T;Sun W;Fan L;Hua C;Wu N;Fan S;Zhang J;Deng X;Yan J
通过指数富集法对铜绿假单胞菌中371个推定的TF进行了高通量的配体系统进化，这导致了199个描述182个TF结合特异性的独特序列基序的稳健富集。通过扫描基因组，我们预测了总共33，709个TF与其靶位点之间的显著相互作用，这些相互作用在基因间区域富集超过11倍，但在基因体区域耗尽。为了进一步探索和阐明TF在铜绿假单胞菌中的生理和致病作用，我们构建了9个主要毒力相关通路的调控网络，发现51个TF与这些毒力通路潜在显著相关，其中32个以前没有被表征过，有些甚至涉及多个通路。这些结果将为今后铜绿假单胞菌及其他相关病原体的转录调控研究提供重要参考，并有助于发现有效的相关传染病治疗和预防策略。
A high-throughput systematic evolution of ligands by exponential enrichment assay was applied to 371 putative TFs in Pseudomonas aeruginosa, which resulted in the robust enrichment of 199 unique sequence motifs describing the binding specificities of 182 TFs. By scanning the genome, we predicted in total 33,709 significant interactions between TFs and their target loci, which were more than 11-fold enriched in the intergenic regions but depleted in the gene body regions. To further explore and delineate the physiological and pathogenic roles of TFs in P. aeruginosa, we constructed regulatory networks for nine major virulence-associated pathways and found that 51 TFs were potentially significantly associated with these virulence pathways, 32 of which had not been characterized before, and some were even involved in multiple pathways. These results will significantly facilitate future studies on transcriptional regulation in P. aeruginosa and other relevant pathogens, and accelerate to discover effective treatment and prevention strategies for the associated infectious diseases.