Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding

Kevin S. Myers, Huihuang D Yan, Irene M. Ong, Dongjun Chung, Kun Liang, Frances Tran, Sündüz Keleş, Robert Landick, Patricia J. Kiley

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

FNR is a well-studied global regulator of anaerobiosis, which is widely conserved across bacteria. Despite the importance of FNR and anaerobiosis in microbial lifestyles, the factors that influence its function on a genome-wide scale are poorly understood. Here, we report a functional genomic analysis of FNR action. We find that FNR occupancy at many target sites is strongly influenced by nucleoid-associated proteins (NAPs) that restrict access to many FNR binding sites. At a genome-wide level, only a subset of predicted FNR binding sites were bound under anaerobic fermentative conditions and many appeared to be masked by the NAPs H-NS, IHF and Fis. Similar assays in cells lacking H-NS and its paralog StpA showed increased FNR occupancy at sites bound by H-NS in WT strains, indicating that large regions of the genome are not readily accessible for FNR binding. Genome accessibility may also explain our finding that genome-wide FNR occupancy did not correlate with the match to consensus at binding sites, suggesting that significant variation in ChIP signal was attributable to cross-linking or immunoprecipitation efficiency rather than differences in binding affinities for FNR sites. Correlation of FNR ChIP-seq peaks with transcriptomic data showed that less than half of the FNR-regulated operons could be attributed to direct FNR binding. Conversely, FNR bound some promoters without regulating expression presumably requiring changes in activity of condition-specific transcription factors. Such combinatorial regulation may allow Escherichia coli to respond rapidly to environmental changes and confer an ecological advantage in the anaerobic but nutrient-fluctuating environment of the mammalian gut.

Original languageEnglish (US)
Article numbere1003565
JournalPLoS Genetics
Volume9
Issue number6
DOIs
StatePublished - Jun 2013

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Transcription Factors
transcription factors
genome
Genome
Escherichia coli
Anaerobiosis
anaerobiosis
binding sites
Binding Sites
protein
operon
Operon
transcriptomics
crosslinking
Immunoprecipitation
lifestyle
anoxic conditions
accessibility
Life Style
Consensus

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding. / Myers, Kevin S.; Yan, Huihuang D; Ong, Irene M.; Chung, Dongjun; Liang, Kun; Tran, Frances; Keleş, Sündüz; Landick, Robert; Kiley, Patricia J.

In: PLoS Genetics, Vol. 9, No. 6, e1003565, 06.2013.

Research output: Contribution to journalArticle

Myers, KS, Yan, HD, Ong, IM, Chung, D, Liang, K, Tran, F, Keleş, S, Landick, R & Kiley, PJ 2013, 'Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding', PLoS Genetics, vol. 9, no. 6, e1003565. https://doi.org/10.1371/journal.pgen.1003565
Myers, Kevin S. ; Yan, Huihuang D ; Ong, Irene M. ; Chung, Dongjun ; Liang, Kun ; Tran, Frances ; Keleş, Sündüz ; Landick, Robert ; Kiley, Patricia J. / Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding. In: PLoS Genetics. 2013 ; Vol. 9, No. 6.
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