High-affinity DNA binding sites for H-NS provide a molecular basis for selective silencing within proteobacterial genomes

TY - JOUR

T1 - High-affinity DNA binding sites for H-NS provide a molecular basis for selective silencing within proteobacterial genomes

AU - Lang, Benjamin

AU - Blot, Nicolas

AU - Bouffartigues, Emeline

AU - Buckle, Malcolm

AU - Geertz, Marcel

AU - Gualerzi, Claudio O.

AU - Mavathur, Ramesh

AU - Muskhelishvili, Georgi

AU - Pon, Cynthia L.

AU - Rimsky, Sylvie

AU - Stella, Stefano

AU - Babu, M. Madan

AU - Travers, Andrew

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=35549009343&partnerID=8YFLogxK

U2 - 10.1093/nar/gkm712

DO - 10.1093/nar/gkm712

M3 - Journal article

C2 - 17881364

AN - SCOPUS:35549009343

SN - 0305-1048

VL - 35

SP - 6330

EP - 6337

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 18

ER -