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H-NS: a universal regulator for a dynamic genome

Key Points

  • Nucleoid-associated proteins in bacteria perform roles that influence all of the major DNA transactions.

  • In Escherichia coli and other Gram-negative bacteria, the H-NS nucleoid-associated protein has a global and negative influence on gene expression. Detailed information is emerging about the mechanisms by which H-NS exerts its negative effects.

  • Knowledge of the domain structure of the H-NS protein is central to the understanding of its biological role. It is becoming clear that the ability of H-NS to oligomerize is of great biological significance.

  • The formation of heteromeric oligomers between related but distinct proteins is a growing theme in studies of H-NS. It is also becoming apparent that H-NS can interact with unrelated proteins.

  • The finding that genes encoding proteins that are capable of interacting with H-NS can be located on mobile genetic elements has potentially important implications for the development and evolution of global regulatory circuits in bacteria.

Abstract

The effect of the bacterial heat-stable nucleoid-structuring (H-NS) protein on gene expression is overwhelmingly negative and extends throughout the genome, pointing to an almost universal role for this nucleoid-associated protein as a transcriptional repressor. Its ability to exert widespread effects on gene expression probably reflects the fact that it binds to curved DNA, which is commonly found at promoters. H-NS and related proteins can engage in both homologous and heterologous protein–protein interactions. Recent data show that the genes that encode H-NS-like proteins can be carried on mobile genetic elements. This raises the possibility that horizontal gene transfer expands the repertoire of protein–protein interactions that nucleoid-associated proteins can engage in, with potentially profound consequences for the global gene-expression profile of the cell.

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Figure 1: Protein-dependent constraint of DNA supercoiling.
Figure 2: H-NS-mediated repression of the virF virulence-gene promoter in Shigella flexneri.
Figure 3: H-NS-mediated trapping of RNA polymerase and antagonism by Fis.
Figure 4: Structure of the H-NS protein.
Figure 5: Two views of H-NS-mediated DNA bridging.
Figure 6: Single-molecule experiments to examine the effect of H-NS binding on DNA structure.

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Acknowledgements

I thank M. Mangan, C. Conway and N. Ní Bhriain for insightful comments on the manuscript. Due to space constraints, it has not been possible to cite every relevant paper and I apologize to colleagues whose work has not been included in the references. Work on bacterial nucleoid-associated proteins in the author's laboratory is supported by Science Foundation Ireland, the Health Research Board and the Wellcome Trust.

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DATABASES

SwissProt

CspA

Fis

FliG

hdfR

Hfq

H-NS

HU

hupA

hupB

IHF

StpA

traJ

YmoA

Glossary

NUCLEOID

In bacteria, the nucleoid is defined as the region that contains the DNA genome and its associated proteins.

PARALOGUES

Sequences, or genes, that have originated from a common ancestral sequence, or gene, by a duplication event.

RNA CHAPERONES

Ubiquitous nucleic-acid-binding proteins that interact with RNA and can promote activities such as RNA–RNA annealing, and strand transfer and exchange.

ANTISENSE RNA

A naturally occurring short, untranslated RNA transcript that often functions as a repressor of plasmid replication.

POLY-(R)-3-HYDROXYBUTYRATE

A lipid homopolymer that is found in association with several membrane and cytoplasmic proteins in E. coli and is a highly efficient solute for many hydrophobic molecules.

PERSISTENCE LENGTH

The average distance over which DNA adopts a straight-line trajectory in three-dimensional space. At distances greater than the persistence length, the DNA adopts a random-coil configuration.

LON-MEDIATED PROTEOLYSIS

Lon is an ATP-dependent protease that is responsible for a large proportion of proteolysis in E. coli.

INCOMPATIBILITY GROUP

All plasmids are grouped into incompatibility groups, that is, groups of plasmids that share similar features and are less stable in the presence of a plasmid from the same group. More than 30 incompatibility groups have been identified.

EPISOME

An independent DNA element, in this case a plasmid, that can replicate extrachromosomally or that can be maintained by integrating into the genome of the host.

α-HAEMOLYSIN TOXIN

A bacterial protein toxin that lyses red blood cells.

PATHOGENICITY ISLAND

A contiguous block of genes, of which at least a subset code for virulence factors.

LOCUS OF ENTEROCYTE EFFACEMENT

(LEE) A chromosomal pathogenicity island in enteropathogenic E. coli that includes the genes responsible for the formation of attachment and effacing (A/E) lesions.

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Dorman, C. H-NS: a universal regulator for a dynamic genome. Nat Rev Microbiol 2, 391–400 (2004). https://doi.org/10.1038/nrmicro883

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