The Fis nucleoid-associated protein controls the expression of a large and diverse regulon of genes in Gram-negative bacteria. Fis production is normally maximal in bacteria during the early exponential phase of batch culture growth, becoming almost undetectable by the onset of stationary phase. We tested the effect on the Fis regulatory network in Salmonella of moving the complete fis gene from its usual location near the origin of chromosomal replication to the position normally occupied by the dps gene in the right macrodomain of the chromosome, and vice versa, creating the gene exchange (GX) strain. In a parallel experiment, we tested the effect of rewiring the Fis regulatory network by placing the fis open reading frame under the control of the stationary-phase-activated dps promoter at the dps genetic location within the right macrodomain, and vice versa, creating the open reading frame exchange (OX) strain. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to measure global Fis protein binding levels and to determine gene expression patterns. Strain GX showed few changes compared with the wild type, although we did detect increased Fis binding at Ter, accompanied by reduced binding at Ori. Strain OX displayed a more pronounced version of this distorted Fis protein-binding pattern together with numerous alterations in the expression of genes in the Fis regulon. OX, but not GX, had a reduced ability to infect cultured mammalian cells. These findings illustrate the inherent robustness of the Fis regulatory network with respect to the effects of rewiring based on gene repositioning alone and emphasize the importance of fis expression signals in phenotypic determination.

中文翻译：

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网络重新布线：相互交换沙门氏菌 fis 和 dps 基因的物理位置和生长阶段依赖性表达模式的生理后果。

Fis 类核相关蛋白控制革兰氏阴性菌中大量多样的基因调节子的表达。在分批培养生长的早期指数阶段，细菌中的 Fis 产量通常最大，在稳定期开始时几乎无法检测到。我们测试了对沙门氏菌Fis 调控网络的影响，将完整的fis基因从其靠近染色体复制起点的通常位置移动到染色体右大域中dps基因通常占据的位置，反之亦然，从而产生基因e x变化 ( GX ) 应变。在平行实验中，我们测试了重新布线 Fis 监管网络的效果，方法是将fis开放阅读框受固定相激活的dps启动子控制，位于右侧宏域内的dps遗传位置，反之亦然，创建开放阅读框 e x变化（OX）应变。染色质免疫沉淀测序 (ChIP-seq) 用于测量全球 Fis 蛋白结合水平并确定基因表达模式。与野生型相比，GX 菌株几乎没有变化，尽管我们确实检测到在 Ter 处的 Fis 结合增加，同时在 Ori 处结合减少。菌株 OX 显示了这种扭曲的 Fis 蛋白结合模式的更明显版本，以及 Fis regulon 中基因表达的许多改变。OX，但不是 GX，感染培养的哺乳动物细胞的能力降低。这些发现说明了 Fis 调控网络在仅基于基因重新定位的重新布线影响方面的内在稳健性，并强调了fis表达信号在表型确定中的重要性。