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

High-affinity DNA binding sites for H-NS provide a molecular basis for selective silencing within proteobacterial genomes.
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DOI:
10.1093/nar/gkm712
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发表时间:
2007
影响因子:
14.9
通讯作者:
Travers A
Travers A
中科院分区:
生物学2区
文献类型:
--
作者:
Lang B;Blot N;Bouffartigues E;Buckle M;Geertz M;Gualerzi CO;Mavathur R;Muskhelishvili G;Pon CL;Rimsky S;Stella S;Babu MM;Travers A

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全局转录调节因子 H-NS 选择性沉默与致病性和环境损害反应相关的细菌基因。尽管有充分的证据表明 H-NS 优先与含有弯曲区域的 DNA 结合,但我们在此表明​​这种选择性的主要基础是 H-NS 靶转录子中存在保守序列基序。我们进一步表明,H-NS 结合位点有强烈的聚集趋势,无论是在操纵子内还是在致病性相关岛中包含的基因中。根据之前发表的研究结果,我们表明这些基序出现在富含 AT 的 DNA 区域。基于这些观察,我们提出 H-NS 通过首先结合成核高亲和力位点然后沿着富含 AT 的 DNA 传播来沉默细菌染色体的广泛区域。这种传播会因该主题在这些地区的频繁出现而得到加强。我们的研究结果表明,这样的组织能够使遗传物质的广泛区域沉默,从而提供一个连贯的框架,统一对 H-NS 蛋白的研究和 H-NS 转录沉默的遗传控制的具体分子基础。
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.
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