New insights into transcriptional regulation by H-NS

Abstract

H-NS, a nucleoid-associated DNA-binding protein of enteric bacteria, was discovered 35 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.

Figure 1. Logo representation of the high-affinity H-NS binding motif

Figure 2. Sequence alignment of the four E.coli H-NS like proteins cited in the text

Structural modularity is evident in this family of gene-regulating proteins. For clarity, sequences have been aligned with the known structures of E. coli H-NS amino- and carboxyl-terminal domains. Models are based on RMN studies of the N- terminal dimer (a) coiled coil interaction and the C-terminal (b) domains of H-NS [3]. A schematic representation of the domain organization of H-NS (c) is aligned with the primary sequence of H-NS, StpA, Hha and Ler. The N-terminal domain contains three alpha helices (α1, α2 and α3). A linker region separating the N and C termini consists of two β strands intercalated between loops 1 and 1′ and loops 1′ and 2 terminating in an α helix and a 3₁₀ α helix that form a nucleic acid binding domain.

Figure 3. Mechanisms of Counter-silencing

Potential mechanisms of counter-silencing include: (A) disruption of H-NS complexes by multimerization antagonists such as H-NST; (B) competition for DNA binding by a high-affinity sequence specific DNA binding protein such as ToxT or RovA; (C) activation of certain promoters such as the E. coli hdeAB promoter by the alternative sigma factor σ^s; (D) changes in promoter geometry due to protein binding or environmental changes that disrupt H-NS complex formation such as may occur at the virF promoter in Shigella. These mechanisms are not mutually exclusive, and it is possible that more than one mechanism may be operating at any given promoter. Reproduced with permission from (38).