Seo Sang Woo, Kim Donghyuk, Latif Haythem, O'Brien Edward J, Szubin Richard, Palsson Bernhard O
1] Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA [2].
Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA.
Nat Commun. 2014 Sep 15;5:4910. doi: 10.1038/ncomms5910.
The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response to iron availability using genome-wide measurements. Integrative data analysis reveals that a total of 81 genes in 42 transcription units are directly regulated by three different modes of Fur regulation, including apo- and holo-Fur activation and holo-Fur repression. We show that Fur connects iron transport and utilization enzymes with negative-feedback loop pairs for iron homeostasis. In addition, direct involvement of Fur in the regulation of DNA synthesis, energy metabolism and biofilm development is found. These results show how Fur exhibits a comprehensive regulatory role affecting many fundamental cellular processes linked to iron metabolism in order to coordinate the overall response of E. coli to iron availability.
铁摄取调节蛋白(Fur)在铁代谢的转录调控中起着关键作用。然而,Fur的全部调控潜力仍不明确。在此,我们利用全基因组测量,全面重建了大肠杆菌K-12 MG1655中响应铁可用性的Fur转录调控网络。综合数据分析表明,42个转录单元中的总共81个基因受到Fur三种不同调控模式的直接调控,包括脱辅基和全铁Fur激活以及全铁Fur抑制。我们表明,Fur通过铁稳态的负反馈环对将铁运输和利用酶联系起来。此外,还发现Fur直接参与DNA合成、能量代谢和生物膜形成的调控。这些结果表明,Fur如何发挥全面的调控作用,影响与铁代谢相关的许多基本细胞过程,以协调大肠杆菌对铁可用性的整体反应。