title: Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli.
abstract: 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.
authors.affiliation: 1] Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA [2].
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Seo
authors.affiliation: 1] Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA [2].
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.affiliation: 1] Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA [2].
authors.forename: Haythem
authors.initials: H
authors.lastname: Latif
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: O'Brien
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Szubin
authors.affiliation: 1] Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA [2] Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark.
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D048168:Escherichia coli K12 / Q000235:genetics* / Q000378:metabolism; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial; D007501:Iron / Q000378:metabolism*; D011485:Protein Binding; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron