A Motif Co-Occurrence Approach for Genome-Wide Prediction of Transcription-Factor-Binding Sites in <i>Escherichia coli</i>

Bulyk, Martha L.; McGuire, Abigail M.; Masuda, Nobuhisa; Church, George M.

doi:10.1101/gr.1448004

Cited by 62 publications

(56 citation statements)

References 49 publications

(58 reference statements)

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“…Additionally, (9) retained nitrate-dependent repression of the P nik promoter (data not shown). Recent bioinformatics approaches to identify transcription factor binding sites in E. coli have not predicted a NarL-binding site in the region of the nik promoter (6,19,23); however, these studies have also not predicted the FNR-binding site (TTGAT-N 4 -AACAG versus consensus TT-GAC-N 4 -ATCAA) in the nik promoter (24,44). These data reveal a role for the high-affinity nickel-binding site in NikR function at low total nickel concentrations.…”

Section: Resultsmentioning

confidence: 87%

Complex Transcriptional Control Links NikABCDE-Dependent Nickel Transport with Hydrogenase Expression in Escherichia coli

2005

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Escherichia coli requires nickel under anaerobic growth conditions for the synthesis of catalytically active NiFe hydrogenases. Transcription of the NikABCDE nickel transporter, which is required for NiFe hydrogenase synthesis, was previously shown to be upregulated by FNR (fumarate-nit rate regulator) in the absence of oxygen and repressed by the NikR repressor in the presence of high extracellular nickel levels. We present here a detailed analysis of nikABCDE transcriptional regulation and show that it closely correlates with hydrogenase expression levels. We identify a nitrate-dependent mechanism for nikABCDE repression that is linked to the NarLX two-component system. NikR is functional under all nickel conditions tested, but its activity is modulated by the total nickel concentration present as well as by one or more components of the hydrogenase assembly pathway. Unexpectedly, NikR function is independent of NikABCDE function, suggesting that NikABCDE is a hydrogenase-specific nickel transporter, consistent with its original identification as a hydrogenase (hyd) mutant. Further, the results suggest that the hydrogenase assembly pathway is sequestered within the cell. A second nickel import pathway in E. coli is implicated in NikR function.Several energetically difficult reactions, such as nitrogen or carbon fixation, are catalyzed by enzymes with complex metal cofactors (26). A striking feature of the synthesis of these enzymes is the requirement of intricate assembly pathways that utilize several protein cofactors to ensure the fidelity of catalytic-site assembly (18). Metalloenzyme expression levels can be tightly regulated in response to changes in environmental conditions; for example, the nitrogenase operon is induced by nitrogen availability but repressed in the presence of oxygen (14). This shifting metabolism, combined with the biosynthetic cost of making these enzymes, means that the transcriptional regulation of these pathways is both necessary and complex. Cells are unlikely to synthesize large quantities of apoenzyme in the absence of the required cofactor(s), just as they are unlikely to expend the energy necessary to synthesize the transporter and accessory proteins necessary for cofactor assembly when the apoenzyme is not being expressed.Escherichia coli exhibits a complex transcriptional response to growth conditions at low oxygen tensions (38). Respiration still occurs, but at lower energetic yield, and it requires the presence of an alternative electron acceptor, such as nitrate, dimethyl sulfoxide (DMSO), trimethylamine oxide (TMAO), or fumarate, and a corresponding terminal reductase (2,16,32,42). E. coli can also ferment carbon sources in the absence of a suitable electron acceptor. E. coli expresses NiFe hydrogenases under anaerobic growth conditions (1, 5, 27, 29, 38) when energetic yields are low, for example, during fermentation or with low-energy-yield electron acceptors such as fumarate. Hydrogenases 1 and 2 (expressed by hya and hyb, respectively) oxidize H 2 in the presence of ...

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Section: Resultsmentioning

confidence: 87%

Complex Transcriptional Control Links NikABCDE-Dependent Nickel Transport with Hydrogenase Expression in Escherichia coli

2005

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“…We propose that AraC bound at this site interacts with additional regulatory proteins, perhaps another monomer of AraC, bound closer to the transcription start site. GalR has been shown to regulate ytfQ (44) (Fig. S1 in the supplemental material).…”

Section: Discussionmentioning

confidence: 99%

Genome-Scale Analyses of Escherichia coli and Salmonella enterica AraC Reveal Noncanonical Targets and an Expanded Core Regulon

et al. 2014

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c Escherichia coli AraC is a well-described transcription activator of genes involved in arabinose metabolism. Using complementary genomic approaches, chromatin immunoprecipitation (ChIP)-chip, and transcription profiling, we identify direct regulatory targets of AraC, including five novel target genes: ytfQ, ydeN, ydeM, ygeA, and polB. Strikingly, only ytfQ has an established connection to arabinose metabolism, suggesting that AraC has a broader function than previously described. We demonstrate arabinose-dependent repression of ydeNM by AraC, in contrast to the well-described arabinose-dependent activation of other target genes. We also demonstrate unexpected read-through of transcription at the Rho-independent terminators downstream of araD and araE, leading to significant increases in the expression of polB and ygeA, respectively. AraC is highly conserved in the related species Salmonella enterica. We use ChIP sequencing (ChIP-seq) and RNA sequencing (RNA-seq) to map the AraC regulon in S. enterica. A comparison of the E. coli and S. enterica AraC regulons, coupled with a bioinformatic analysis of other related species, reveals a conserved regulatory network across the family Enterobacteriaceae comprised of 10 genes associated with arabinose transport and metabolism.

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“…The integration of sequence and structural data yields insights into the structural basis of TF cooperativity, suggesting that enhanceosome-like binding is widespread in conserved non-coding elements that are predominantly distal to genes. This work expands on previous studies of TF cooperativity based on motif co-occurrence [19,20,[41][42][43]. First, previous approaches have typically excluded overlapping motif arrangements [20,42,44], which have been shown to be both critical to the mechanisms of enhancer function [14] and, as our screen suggests, quite abundant.…”

Section: Discussionmentioning

confidence: 59%

“…While this step may seem overly conservative, it significantly reduces the predictions' FDR. The less likely to be functional motif arrangements (163 654 in this study; figure 1c) we remove this way may well go unnoticed when using uniform null co-occurrence distributions [19,20].…”

Section: Discussionmentioning

confidence: 97%

Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

Guturu

Doxey

Wenger

et al. 2013

Phil. Trans. R. Soc. B

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Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis -regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF–TF–DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein–protein interactions, potentially indirect interactions and ‘through-DNA’ interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex .

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A Motif Co-Occurrence Approach for Genome-Wide Prediction of Transcription-Factor-Binding Sites in Escherichia coli

Cited by 62 publications

References 49 publications

Complex Transcriptional Control Links NikABCDE-Dependent Nickel Transport with Hydrogenase Expression in Escherichia coli

Complex Transcriptional Control Links NikABCDE-Dependent Nickel Transport with Hydrogenase Expression in Escherichia coli

Genome-Scale Analyses of Escherichia coli and Salmonella enterica AraC Reveal Noncanonical Targets and an Expanded Core Regulon

Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

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