H-NS: a universal regulator for a dynamic genome

Dorman, Charles J.

doi:10.1038/nrmicro883

Cited by 485 publications

(525 citation statements)

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“…H-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.…”

Section: H-ns--a Nucleoid Proteinmentioning

confidence: 99%

“…H-NS was regarded for many years as a DNA binding protein without a specific consensus sequence for binding, and the well-known ability of H-NS to affect a wide range of genes was attributed to a preference for particular DNA structures [1]. H-NS recognition sites typically display planar curvature specified by AT-rich motifs, as commonly found at promoters.…”

Section: Recognition Of Dna By H-nsmentioning

confidence: 99%

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New insights into transcriptional regulation by H-NS

Fang

Rimsky

2008

Current Opinion in Microbiology

183

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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Section: H-ns--a Nucleoid Proteinmentioning

confidence: 99%

Section: Recognition Of Dna By H-nsmentioning

confidence: 99%

New insights into transcriptional regulation by H-NS

Fang

Rimsky

2008

Current Opinion in Microbiology

183

173

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“…H-NS is a small (137 aa) but abundant protein (approximately 2610 4 molecules per cell) (Ussery et al, 1994;Rimsky, 2004;Dorman, 2004). It is a global regulator which controls the expression of a large number of genes whose products are involved in a wide range of cellular processes (Ussery et al, 1994;Rimsky, 2004;Dorman, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…It is a global regulator which controls the expression of a large number of genes whose products are involved in a wide range of cellular processes (Ussery et al, 1994;Rimsky, 2004;Dorman, 2004). In pathogenic enteric bacteria, such as enteropathogenic E. coli (EPEC) (Bustamante et al, 2001;Haack et al, 2003), ETEC (Murphree et al, 1997), enteroinvasive E. coli (Falconi et al, 2001), Shigella flexneri (Porter & Dorman, 1994) and Vibrio cholerae (Nye et al, 2000;Yu & DiRita, 2002), H-NS participates in the regulation of virulence gene expression.…”

Section: Introductionmentioning

confidence: 99%

The H-NS protein represses transcription of the eltAB operon, which encodes heat-labile enterotoxin in enterotoxigenic Escherichia coli, by binding to regions downstream of the promoter

et al. 2005

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Heat-labile enterotoxin, a major virulence determinant of enterotoxigenic Escherichia coli, is encoded by the eltAB operon. To elucidate the molecular mechanism by which the heat-stable nucleoid-structural (H-NS) protein controls transcription of eltAB, the authors constructed an eltAB-lacZ transcriptional fusion and performed b-galactosidase analysis. The results showed that H-NS protein exerts fivefold repression on transcription from the eltAB promoter at 37 6C and 10-fold repression at 22 6C. Two silencer regions that were required for H-NS-mediated repression of eltAB expression were identified, both of which were located downstream of the start site of transcription. One silencer was located between +31 and +110, the other between +460 and +556, relative to the start site of transcription, and they worked cooperatively in repression. DNA sequences containing the silencers were predicted to be curved by in silico analysis and bound H-NS protein directly in vitro. Repression of eltAB transcription by H-NS was independent of promoter strength, and the presence of H-NS protein did not affect promoter opening in vitro, indicating that repression was achieved by inhibiting promoter clearance or blocking transcription elongation, probably via DNA looping between the two silencers.

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“…H-NS has most extensively been studied in E. coli and it appears to exist to turn genes off (Dorman 2004). H-NS has affinity for all types of nucleic acids but binds preferentially to intrinsically curved DNA, which is commonly found at promoters, and can alter DNA topology by constraining negative supercoiling (Owen-Hughes et al 1992).…”

Section: Finding and Validating New Drug Targets In M Tuberculosismentioning

confidence: 99%