Stoebel Daniel M, Free Andrew, Dorman Charles J
Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
Institute of Evolutionary Biology, University of Edinburgh, Room 714a, Darwin Building, The King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
Microbiology (Reading). 2008 Sep;154(Pt 9):2533-2545. doi: 10.1099/mic.0.2008/020693-0.
The H-NS nucleoid-associated DNA-binding protein is an important global repressor of transcription in Gram-negative bacteria. Recently, H-NS has been implicated in the process of xenogeneic silencing, where it represses the transcription of foreign genes acquired by horizontal transfer. This raises interesting questions about the integration of the horizontally acquired genes into the existing gene regulatory networks of the microbe. In particular, how do bacteria derepress silenced genes in order to benefit from their expression without compromising competitive fitness through doing so inappropriately? This article reviews current knowledge about the derepression of genes that are transcriptionally silenced by H-NS. It describes a variety of anti-silencing mechanisms involving (i) protein-independent processes that operate at the level of local DNA structure, (ii) DNA-binding proteins such as Ler, LeuO, RovA, SlyA, VirB, and proteins related to AraC, and (iii) modulatory mechanisms in which H-NS forms heteromeric protein-protein complexes with full-length or partial paralogues such as StpA, Sfh, Hha, YdgT, YmoA or H-NST. The picture that emerges is one of apparently ad hoc solutions to the problem of H-NS-mediated silencing, suggesting that microbes are capable of evolving anti-silencing methods based on the redeployment of existing regulatory proteins rather than employing dedicated, bespoke antagonists. There is also evidence that in a number of cases more sophisticated regulatory processes have been superimposed on these rather simple anti-silencing mechanisms, broadening the range of environmental signals to which H-NS-repressed genes respond.
H-NS核仁相关DNA结合蛋白是革兰氏阴性菌中一种重要的全局转录抑制因子。最近,H-NS与异源沉默过程有关,在该过程中它抑制通过水平转移获得的外源基因的转录。这就引发了关于水平获得的基因如何整合到微生物现有基因调控网络中的有趣问题。特别是,细菌如何解除对沉默基因的抑制,以便从其表达中受益,同时又不会因不适当的解除抑制而损害竞争适应性?本文综述了目前关于被H-NS转录沉默的基因的去抑制的知识。它描述了多种抗沉默机制,包括(i)在局部DNA结构水平上起作用的不依赖蛋白质的过程,(ii)DNA结合蛋白,如Ler、LeuO、RovA、SlyA、VirB以及与AraC相关的蛋白质,(iii)H-NS与全长或部分旁系同源物(如StpA、Sfh、Hha、YdgT、YmoA或H-NST)形成异源蛋白-蛋白复合物的调节机制。呈现出的情况是,对于H-NS介导的沉默问题,似乎是临时解决方案,这表明微生物能够基于现有调控蛋白的重新部署来进化抗沉默方法,而不是采用专门定制的拮抗剂。也有证据表明,在许多情况下,更复杂的调控过程叠加在这些相当简单的抗沉默机制之上,拓宽了H-NS抑制基因所响应的环境信号范围。