Seo, Sang Woo4; Kim, Donghyuk4; Latif, Haythem4; O'Brien, Edward J.4; Szubin, Richard4; Palsson, Bernhard1
1 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2 Genome Scale CHO in Silico Models & their Application, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3 Network Reconstruction in Silico Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4 University of California, San Diego
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.