title: High-affinity DNA binding sites for H-NS provide a molecular basis for selective silencing within proteobacterial genomes.
abstract: The global transcriptional regulator H-NS selectively silences bacterial genes associated with pathogenicity and responses to environmental insults. Although there is ample evidence that H-NS binds preferentially to DNA containing curved regions, we show here that a major basis for this selectivity is the presence of a conserved sequence motif in H-NS target transcriptons. We further show that there is a strong tendency for the H-NS binding sites to be clustered, both within operons and in genes contained in the pathogenicity-associated islands. In accordance with previously published findings, we show that these motifs occur in AT-rich regions of DNA. On the basis of these observations, we propose that H-NS silences extensive regions of the bacterial chromosome by binding first to nucleating high-affinity sites and then spreading along AT-rich DNA. This spreading would be reinforced by the frequent occurrence of the motif in such regions. Our findings suggest that such an organization enables the silencing of extensive regions of the genetic material, thereby providing a coherent framework that unifies studies on the H-NS protein and a concrete molecular basis for the genetic control of H-NS transcriptional silencing.
authors: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
authors: Benjamin
authors: B
authors: Lang
authors: Nicolas
authors: N
authors: Blot
authors: Emeline
authors: E
authors: Bouffartigues
authors: Malcolm
authors: M
authors: Buckle
authors: Marcel
authors: M
authors: Geertz
authors: Claudio O
authors: CO
authors: Gualerzi
authors: Ramesh
authors: R
authors: Mavathur
authors: Georgi
authors: G
authors: Muskhelishvili
authors: Cynthia L
authors: CL
authors: Pon
authors: Sylvie
authors: S
authors: Rimsky
authors: Stefano
authors: S
authors: Stella
authors: M Madan
authors: MM
authors: Babu
authors: Andrew
authors: A
authors: Travers
mesh_terms: D020856:AT Rich Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D016680:Genome, Bacterial; D044404:Genomic Islands; D023281:Genomics; D009876:Operon; D020560:Proteobacteria / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C031908:H-NS protein, bacteria