揭示 RpoD 家族σ因子在鼠伤寒沙门氏菌热休克反应中的新型调控作用的系统生物学研究。
Unveiling the novel regulatory roles of RpoD-family sigma factors in Salmonella Typhimurium heat shock response through systems biology approaches.
机构信息
School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
出版信息
PLoS Genet. 2024 Oct 29;20(10):e1011464. doi: 10.1371/journal.pgen.1011464. eCollection 2024 Oct.
Three RpoD-family sigma factors, RpoD, RpoS, and RpoH, play critical roles in transcriptional regulation in Salmonella enterica serovar Typhimurium under heat shock conditions. However, the genome-wide regulatory mechanisms of these sigma factors in response to heat stress have remained elusive. In this study, we comprehensively identified 2,319, 2,226, and 213 genome-wide binding sites for RpoD, RpoS, and RpoH, respectively, under sublethal heat shock conditions (42°C). Machine learning-based transcriptome analysis was employed to infer the relative activity of iModulons, providing valuable insights into the transcriptional impact of heat shock. Integrative data analysis enabled the reconstruction of the transcriptional regulatory network of sigma factors, revealing how they modulate gene expression to adapt to heat stress, including responses to anaerobic and oxidative stresses. Notably, we observed a significant expansion of the RpoS sigmulon from 97 to 301 genes in response to heat shock, underscoring the crucial role of RpoS in regulating various metabolic processes. Moreover, we uncovered a competition mechanism between RpoD and RpoS within RpoS sigmulons, where RpoS significantly increases its binding within promoter regions shared with RpoD under heat shock conditions. These findings illuminate how three RpoD-family sigma factors coordinate multiple cellular processes to orchestrate the overall response of S. Typhimurium to heat stress.
三种 RpoD 家族σ因子(RpoD、RpoS 和 RpoH)在鼠伤寒沙门氏菌的热休克条件下的转录调控中发挥着关键作用。然而,这些σ因子在热应激下的全基因组调控机制仍然难以捉摸。在这项研究中,我们在亚致死热休克条件(42°C)下,分别全面鉴定了 2319、2226 和 213 个 RpoD、RpoS 和 RpoH 的全基因组结合位点。基于机器学习的转录组分析被用来推断 iModulons 的相对活性,这为热休克的转录影响提供了有价值的见解。综合数据分析能够重建σ因子的转录调控网络,揭示它们如何调节基因表达以适应热应激,包括对厌氧和氧化应激的反应。值得注意的是,我们观察到 RpoS sigmulon 从 97 个基因显著扩展到 301 个基因,以响应热休克,这突出了 RpoS 在调节各种代谢过程中的关键作用。此外,我们在 RpoS sigmulons 中发现了 RpoD 和 RpoS 之间的竞争机制,在热休克条件下,RpoS 在与 RpoD 共享的启动子区域中显著增加其结合。这些发现阐明了三种 RpoD 家族σ因子如何协调多个细胞过程,以协调鼠伤寒沙门氏菌对热应激的整体反应。