Unveiling the novel regulatory roles of RpoD-family sigma factors in Salmonella Typhimurium heat shock response through systems biology approaches.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2024-10-29 eCollection Date: 2024-10-01 DOI:10.1371/journal.pgen.1011464
Joon Young Park, Minchang Jang, Sang-Mok Lee, Jihoon Woo, Eun-Jin Lee, Donghyuk Kim
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引用次数: 0

Abstract

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.

通过系统生物学方法揭示 RpoD 家族 sigma 因子在鼠伤寒沙门氏菌热休克反应中的新型调控作用。
在热休克条件下,肠炎沙门氏菌(Salmonella enterica serovar Typhimurium)的三个 RpoD 家族 sigma 因子 RpoD、RpoS 和 RpoH 在转录调控中发挥着关键作用。然而,这些σ因子在热应激反应中的全基因组调控机制仍然难以捉摸。在本研究中,我们全面鉴定了亚致死热休克条件(42°C)下 RpoD、RpoS 和 RpoH 分别有 2319、2226 和 213 个全基因组结合位点。利用基于机器学习的转录组分析来推断 iModulons 的相对活性,为了解热休克对转录的影响提供了宝贵的信息。通过整合数据分析,我们重建了西格玛因子的转录调控网络,揭示了它们如何调节基因表达以适应热休克,包括对厌氧和氧化休克的反应。值得注意的是,我们观察到在热休克反应中,RpoS sigmulon 从 97 个基因显著扩展到 301 个基因,这凸显了 RpoS 在调节各种代谢过程中的关键作用。此外,我们还发现了 RpoD 和 RpoS 在 RpoS sigmulons 中的竞争机制,即在热休克条件下,RpoS 在与 RpoD 共享的启动子区域内的结合显著增加。这些发现阐明了三个 RpoD 家族西格玛因子如何协调多个细胞过程,以协调伤寒杆菌对热应激的整体反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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