Association of nucleoid proteins with coding and non-coding segments of the Escherichia coli genome

Grainger, David C.; Hurd, Douglas; Goldberg, Martin D.; Busby, Stephen J. W.

doi:10.1093/nar/gkl542

Cited by 266 publications

(325 citation statements)

References 39 publications

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“…High-affinity binding sites have also been reported with the current paradigm because they serve as initiation sites for nucleation of H-NS to form higher-order nucleoprotein structures (6). H-NS is responsible for binding and repressing >400 genes in Salmonella (4, 7) and in Escherichia coli (8,9), many of which are DNA sequences obtained through horizontal gene transfer and involved in adaptive stress responses and virulence (10). Numerous phenotypes associated with hns mutations have been described, and the effects of H-NS on gene expression are largely inhibitory (2,11), which is partially explained by the ability of H-NS to bridge adjacent helices of DNA (12,13), causing either the trapping or the occlusion of RNA polymerase in the promoter regions (2,14).…”

Section: H-ns | Virulencementioning

confidence: 99%

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes inMycobacterium tuberculosis

Gordon

Li²,

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

191

250

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Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a unique nucleoid-associated protein that binds AT-rich regions of the genome, including genomic islands acquired by horizontal gene transfer and regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM and PGL, and the PE/PPE families of antigenic proteins. Comparison of genome-wide binding data with expression data indicates that Lsr2 binding results in transcriptional repression. Domain-swapping experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C-terminal DNA-binding domain. Nuclear magnetic resonance analysis of the DNA-binding domain of Lsr2 and its interaction with DNA reveals a unique structure and a unique mechanism that enables Lsr2 to discriminately target AT-rich sequences through interactions with the minor groove of DNA. Taken together, we provide evidence that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve a function similar to the Enterobacteriaceae H-NS, likely coordinating global gene regulation and virulence in this group of medically important bacteria.

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Section: H-ns | Virulencementioning

confidence: 99%

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes inMycobacterium tuberculosis

Gordon

Li²,

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

191

250

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“…From the genome-wide mapping results, we were also able to show that: (i) A total of 138 Lrp-binding regions were identified, Ϸ84% of which were located within noncoding regions, whereas the remaining Ϸ16% were found within coding regions; (ii) 34 and 92 Lrp-binding regions were identified in exponentially growing cells in the presence and absence of exogenous leucine, respectively, indicating that Lrp bindings to the E. coli genome are dramatically sensitive to the addition of exogenous leucine; and (iii) the Lrp-binding sites on the E. coli genome under stationary growth condition (134 Lrp-binding regions identified) indicated that Lrp plays pivotal roles in the transcriptional regulation under stationary growth conditions. The high number of Lrp-binding regions was not surprising, given that global transcription factors such as Fnr, Crp, Ihf, Fis, and Hns specifically bind to between Ϸ63 and Ϸ224 target regions (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Genome-scale reconstruction of the Lrp regulatory network in Escherichia coli

Cho

Barrett

Knight

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

162

225

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Broad-acting transcription factors (TFs) in bacteria form regulons. Here, we present a 4-step method to fully reconstruct the leucineresponsive protein (Lrp) regulon in Escherichia coli K-12 MG 1655 that regulates nitrogen metabolism.Step 1 is composed of obtaining high-resolution ChIP-chip data for Lrp, the RNA polymerase and expression profiles under multiple environmental conditions. We identified 138 unique and reproducible Lrp-binding regions and classified their binding state under different conditions. In the second step, the analysis of these data revealed 6 distinct regulatory modes for individual ORFs. In the third step, we used the functional assignment of the regulated ORFs to reconstruct 4 types of regulatory network motifs around the metabolites that are affected by the corresponding gene products. In the fourth step, we determined how leucine, as a signaling molecule, shifts the regulatory motifs for particular metabolites. The physiological structure that emerges shows the regulatory motifs for different amino acid fall into the traditional classification of amino acid families, thus elucidating the structure and physiological functions of the Lrp-regulon. The same procedure can be applied to other broad-acting TFs, opening the way to full bottom-up reconstruction of the transcriptional regulatory network in bacterial cells. ChIP-chip ͉ transcription factorT ranscriptional regulatory systems often regulate the formation rates and the concentration of small molecules by 2 feedback loops that regulate the transporters and metabolic enzymes. In many cases, these 2 feedback loops are connected by a common transcription factor (TF) that senses the concentration of the small molecule (1). Little is known at present about the transition between the regulatory modes in the feedback loop motifs for global TFs in bacteria. One such transcription factor is the leucineresponsive protein (Lrp), which is a global transcription regulator widely distributed throughout the bacteria including Escherichia coli (2-4). The Lrp regulon includes genes involved in amino acid biosynthesis and degradation, small molecule transport, pili synthesis, and other cellular functions including 1-carbon metabolism (2, 4-6). The regulatory action of Lrp on target genes is often modulated by the binding of the small effector molecule leucine and in effect endows Lrp with the ability to affect transcriptional regulation in all possible ways. That is, upon addition of leucine to the environment, the activity of Lrp can be enhanced, reversed, or unaffected (2, 4, 7). Little is known about in vivo Lrp-binding events at the genome scale in the presence or absence of leucine and the extent to which the different modes of regulation are used for different metabolites. Such information is needed to reconstruct the Lrp regulon and the understanding of nitrogen metabolism.In this study, we applied a systems approach by integrating genome-scale data from chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) for Lrp and...

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“…Most well studied are the H-NS proteins from Escherichia coli and Salmonella enterica sv. Typhimurium (S. Typhimurium) where genome-wide ChIPchip and microarray studies have identified the set of genes under H-NS repression (4,6,9). In S. Typhimurium, H-NS regulates over 400 genes, including Salmonella pathogenicity islands 1-5 (SPI1 to -5) 4 (4,5).…”

Section: The Bacterial Nucleoid-associated Proteins Hha and H-ns Joinmentioning

confidence: 99%

Structural Insights into the Regulation of Foreign Genes in Salmonella by the Hha/H-NS Complex

Ali

Whitney

Stevenson

et al. 2013

Journal of Biological Chemistry

108

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Association of nucleoid proteins with coding and non-coding segments of the Escherichia coli genome

Cited by 266 publications

References 39 publications

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes inMycobacterium tuberculosis

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes inMycobacterium tuberculosis

Genome-scale reconstruction of the Lrp regulatory network in Escherichia coli

Structural Insights into the Regulation of Foreign Genes in Salmonella by the Hha/H-NS Complex

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