Expression of Salmonella enterica loci harboring undermethylated GATC sites at promoters or regulatory regions was monitored by single cell analysis. Cell-to-cell differences in expression were detected in ten such loci (carA, dgoR, holA, nanA, ssaN, STM1290, STM3276, STM5308, gtr and opvAB), with concomitant formation of ON and OFF subpopulations. The ON and OFF subpopulation sizes varied depending on the growth conditions, suggesting that the population structure can be modulated by environmental control. All the loci under study except STM5308 displayed altered patterns of expression in strains lacking or overproducing Dam methylase, thereby confirming control by Dam methylation. Bioinformatic analysis identified potential binding sites for transcription factors OxyR, CRP and Fur, and analysis of expression in mutant backgrounds confirmed transcriptional control by one or more of such factors. Surveys of gene expression in pairwise combinations of Dam methylation-dependent loci revealed independent switching, thus predicting the formation of a high number of cell variants. This study expands the list of S. enterica loci under transcriptional control by Dam methylation, and underscores the relevance of the DNA adenine methylome as a source of phenotypic heterogeneity.

中文翻译：

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DNA腺嘌呤甲基化对肠沙门氏菌基因表达异质性的贡献。

通过单细胞分析监测在启动子或调节区中携带甲基化不足的GATC位点的肠炎沙门氏菌基因座的表达。在十个这样的基因座（carA，dgoR，holA，nanA，ssaN，STM1290，STM3276，STM5308，gtr和opvAB）中检测到细胞间表达差异，并同时形成ON和OFF亚群。ON和OFF子种群的大小取决于生长条件，这表明可以通过环境控制来调节种群结构。除STM5308外的所有研究基因座在缺乏或过量产生Dam甲基化酶的菌株中，显示出改变的表达模式，从而证实了Dam甲基化的控制。生物信息学分析确定了转录因子OxyR，CRP和Fur的潜在结合位点，突变背景中的表达分析证实了一种或多种此类因子对转录的控制。Dam甲基化依赖性基因座的成对组合中的基因表达调查显示独立的转换，从而预测了大量细胞变异的形成。这项研究扩大了通过达姆甲基化进行转录控制的肠炎链球菌基因座，并强调了DNA腺嘌呤甲基化作为表型异质性来源的相关性。