New insights into transcriptional regulation by H-NS

Abstract

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...

A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii

“…3 A and B). H-NS proteins are a family of global regulators that bind A-T-rich regions and are usually used to silence horizontally acquired genes (30). Proteins within the H-NS family have been suggested to be involved in T6SS regulation (31,32).…”

Modulation of Rho-Dependent Transcription Termination in Escherichia coli by the H-NS Family of Proteins

“…The ability of H-NS to influence nucleoid structure and gene expression at the level of transcription initiation has been variously attributed to its different yet inter-related mechanistic properties, including those of high-affinity and low-affinity DNA binding, assembly into a polymeric scaffold, and induction of alterations in DNA architecture such as bending, bridging, stiffening, coating, looping, and supercoiling (16,20,23,32,39,61). H-NS has also been implicated in direct RNA binding and translational regulation (41).…”

“…The presence of the two dimerization interfaces allows H-NS to assemble (either alone or with its paralogous partner StpA [53,55,60,65,67]) into a helical polymeric scaffold around which DNA is bound (3,22). Binding of H-NS to DNA results in several structural (including supercoiling) alterations that have been variously referred to as bending, bridging, coating, looping, and stiffening of the DNA (16,20,23,32,39,61). YdgT and Hha bear structural resemblance to, and also interact with, the N-terminal oligomerization domains of H-NS and StpA; in this manner, YdgT and Hha are believed to modulate the DNA-binding and nucleoid-organizing properties of H-NS and StpA even though they do not bind DNA by themselves (23,30,33,38,42,55).…”

Anti-silencing: overcoming H-NS-mediated repression of transcription in Gram-negative enteric bacteria

“…The result has been described as H-NSmediated transcriptional silencing (Bouffartigues et al, 2007;Fang & Rimsky, 2008;Göransson et al, 1990;Lang et al, 2007;Lucchini et al, 2006;Madhusudan et al, 2005;McGovern et al, 1994;Murphree et al, 1997;Navarre et al, 2006;Nye et al, 2000;Petersen et al, 2002;Westermark et al, 2000;Will et al, 2004). It has been estimated from single-molecule studies using optical tweezers that the force required to disrupt an H-NS-DNA bridge is 7 pN at an unzipping rate of 70 bp s 21 , which is the speed of RNA polymerase; RNA polymerase can exert a force of up to 25 pN (Dame et al, 2006).…”