H‐NS: a modulator of environmentally regulated gene expression

Atlung, Tove; Ingmer, Hanne

doi:10.1046/j.1365-2958.1997.3151679.x

Cited by 453 publications

(431 citation statements)

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“…H-NS has long been regarded as a global modulator of gene expression in response to pH, temperature, osmolarity and growth phase [14][15][16]. A large proportion of Salmonella genes induced upon temperature shift from 25°C to 37°C are dependent on H-NS [17], an effect attributed to putative conformational changes in H-NS and reduced DNA binding.…”

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“…Moreover, H-NS oligomerization has been reported to be higher at 37°C than 25°C [18] and uninfluenced by further temperature increases to 48°C or pH variation between 4.0 and 9.0. Similarly, while H-NS represses the transcription of a number of osmoregulated genes [14], many H-NS-silenced genes are unaffected by changes in osmolarity. These observations indicate that the relationship between H-NS and environmentally dependent alterations in gene expression is complex, and that H-NS should not be viewed as a simple temperature or osmolarity sensor.…”

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New insights into transcriptional regulation by H-NS

Fang

Rimsky

2008

Current Opinion in Microbiology

186

173

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H-NS, a nucleoid-associated DNA-binding protein of enteric bacteria, was discovered thirty-five years ago and subsequently found to exert widespread and highly pleiotropic effects on gene regulation. H-NS binds to high-affinity sites and spreads along adjacent AT-rich DNA to silence transcription. Preferential binding to sequences with higher AT-content than the resident genome allows H-NS to repress the expression of foreign DNA in a process known as "xenogeneic silencing." Counter-silencing by a variety of mechanisms facilitates the evolutionary acquisition of horizontally transferred genes and their integration into pre-existing regulatory networks. This review will highlight recent insights into the mechanism and biological importance of H-NS-DNA interactions. H-NS--A Nucleoid ProteinH-NS is an abundant DNA-binding protein implicated in the organization of the bacterial chromosome [1]. H-NS and other nucleoid-associated proteins can affect DNA topology at specific loci, thereby modulating gene transcription. Binding by these proteins is proposed to selectively direct supercoiling effects to promoters [2•]. Mutation of hns alters the responsiveness of transcription to changes in DNA superhelicity. Regulatory effects of supercoiling are linked to metabolic and environmental conditions. Thus, H-NS has been viewed as a nucleoid structuring protein with global effects on gene expression [3].H-NS exists primarily as a dimer at low concentrations but can multimerize into higher order complexes [4,5] that form bridges between adjacent DNA helices [6]. Optical tweezers have been used to demonstrate that H-NS dimers or multimers can simultaneously interact with separate DNA binding sites [7••]. H-NS-coated DNA is not self-interactive, suggesting that dimerization or oligomerization must precede DNA binding for bridging to occur. Force measurements suggest that transcription barriers created by H-NS binding are weak (∼7 pN) and readily overcome, so that H-NS oligomers pose only a relative barrier to translocating RNA polymerase. DNA bridging is a conserved feature of H-NS homologs found in most gram-negative bacteria [8] that appears to constrain large DNA loops [9••] and helps to account for the effects of H-NS on transcription. However, it must be noted that the relationship between bridging as a general effect and the silencing of specific promoters is not yet clear.H-NS is more appropriately viewed as a determinant of chromosomal architecture rather than as a general structural component. The analysis of nucleoids treated with urea suggests that *Corresponding Author : Tel 206-275-0966, Fax 206-616-1575, e-mail : fcfang@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production proce...

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New insights into transcriptional regulation by H-NS

Fang

Rimsky

2008

Current Opinion in Microbiology

186

173

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“…Some of these complexes are assembled by architectural elements that by analogy to eukaryotic systems are referred to as histone-like proteins. In Escherichia coli, the major constituents of bacterial nucleoid are the HU heterodimer [reviewed in Drlica and Rouviere-Yaniv (1987)] and H-NS [reviewed in Ussery et al (1994) and Atlung and Ingmer (1997)]. These proteins are small, very abundant, and bind DNA with little or no sequence specificity, usually through the minor groove.…”

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Phage Ø29 Protein p6 Is in a Monomer−Dimer Equilibrium That Shifts to Higher Association States at the Millimolar Concentrations Found in Vivo

et al. 1997

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Protein p6 from Bacillus subtilis phage Ø29 (M r ) 11 800) binds in Vitro to DNA forming a large nucleoprotein complex in which the DNA wraps a multimeric protein core. The high intracellular abundance of protein p6 together with its ability to bind the whole Ø29 DNA in Vitro strongly suggests that it plays a role in viral genome organization. We have determined by sedimentation equilibrium analysis that protein p6 (1-100 µM range), in the absence of DNA, is in a monomer-dimer equilibrium, with an association constant (K 2 ) of ∼2 × 10 5 M -1 . The intracellular concentration of protein p6 (∼1 mM) was estimated measuring the number of copies per cell (7 × 10 5 ) and the cell volume (1 × 10 -15 L). At concentrations around 1 mM, protein p6 associates into oligomers. This self-association behavior is compatible with a dimer-hexamer model (K 2,6 ) 3.2 × 10 8 M -2 ) or with an isodesmic association of the dimer (K ) 950 M -1 ), because the apparent weight-average molecular mass (M w,a ) does not reach saturation at the highest protein concentrations. The sedimentation coefficients of protein p6 monomer and dimer were 1.4 and 2.0, respectively, compatible with translational frictional ratios (f/f o ) of 1.15 and 1.30, which slightly deviate from the hydrodynamics of a rigid globular protein. Taking together these results and considering the structure of the nucleoprotein complex, we speculate that the observed oligomers of protein p6 could mimic a scaffold on which DNA folds to form the nucleoprotein complex in ViVo.The genomes of prokaryotic organisms are organized in higher order nucleoprotein complexes that, besides a packaging role, mediate fundamental processes of DNA such as replication, transcription, recombination, and transposition (Echols, 1990). Some of these complexes are assembled by architectural elements that by analogy to eukaryotic systems are referred to as histone-like proteins. In Escherichia coli, the major constituents of bacterial nucleoid are the HU heterodimer [reviewed in Drlica and Rouviere-Yaniv (1987)] and H-NS [reviewed in Ussery et al. (1994) and Atlung and Ingmer (1997)]. These proteins are small, very abundant, and bind DNA with little or no sequence specificity, usually through the minor groove. The pleiotropic nature of mutations in their corresponding genes indicates that these proteins have multiple functions. HU is reported to be involved in replication, transposition, and transcriptional control, while H-NS has been suggested to be a modulator of regulated gene expression.Protein p6 from Bacillus subtilis phage Ø29 has some features resembling those expected for a histone-like protein.Protein p6 is the most abundant protein in Ø29-infected cells and binds in Vitro to the viral DNA forming multiple complexes spread virtually throughout the entire genome, of sizes ranging from ∼100 base pairs (bp) up to ∼2 kilobases (kb) (Gutiérrez et al., 1994). Protein p6 binds to DNA through the minor groove, and it does not recognize a specific sequence, but rather a DNA structural f...

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“…Mutations in hns -the gene that encodes H-NS -are highly pleiotropic. Many of the H-NS-modulated genes are related to adaptation to environmental conditions and/or virulence (Atlung & Ingmer 1997, Hommais et al 2001). H-NS has been shown to be involved in repression of the virF virulence-gene promoter Shigella flexneri, a facultative intracellular pathogen (Falconi et al 1998).…”

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confidence: 99%