Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

Sang Woo Seo, Donghyuk Kim, Haythem Latif, Edward J. O'Brien, Richard Szubin, Bernhard Palsson

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalNature Communications
Volume5
Number of pages10
ISSN2041-1723
DOIs
Publication statusPublished - 2014

Keywords

  • MULTIDISCIPLINARY
  • SINGLE-NUCLEOTIDE RESOLUTION
  • GENOME-SCALE RECONSTRUCTION
  • STAPHYLOCOCCUS-AUREUS
  • GENE-REGULATION
  • EXPRESSION
  • DNA
  • HOMEOSTASIS
  • REGULON
  • BINDING
  • IDENTIFICATION

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