Regulon and promoter analysis of the E-coli heat-shock factor, σ32, reveals a multifaceted cellular response to heat stress
Regulon and promoter analysis of the E-coli heat-shock factor, σ32, reveals a multifaceted cellular response to heat stress
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DOI：
10.1101/gad.1428206
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发表时间：
2006-07-01
影响因子：
10.5
通讯作者：
Rhodius, Virgil A.
中科院分区：
文献类型：
--
作者：
Nonaka, Gen;Blankschien, Matthew;Rhodius, Virgil A.
热休克反应（HSR）是细胞对热的一种普遍反应，对细胞的适应至关重要。在大肠杆菌中，HSR由替代σ因子σ介导（32）。为了确定其作用，我们使用全基因组表达分析和启动子验证来鉴定由sigma（32）直接调控的基因，并筛选ORF过表达文库来鉴定sigma（32）诱导剂。我们将经sigma验证可转录的基因数量增加了三倍（32）。并为这种反应的细胞作用提供了新的见解。我们的工作表明，这种反应是随着调节子编码许多全局转录调节因子而传播的，揭示了sigma（70）全酶起始于12%的sigma（32）启动子，这对全局转录连接具有重要意义，并确定了蛋白质稳态反应的新作用，即保护复杂蛋白质。最后，这项研究表明，反应保护细胞膜，并响应其状态：整整25%的sigma（32）调节子成员驻留在膜上，并改变其功能;此外，诱导反应的过度表达蛋白质的比例不成比例的膜定位。反应与细胞膜的紧密联系解释了为什么反应的主要调节因子位于细胞室中。
The heat-shock response (HSR), a universal cellular response to heat, is crucial for cellular adaptation. In Escherichia coli, the HSR is mediated by the alternative sigma factor, sigma(32). To determine its role, we used genome-wide expression analysis and promoter validation to identify genes directly regulated by sigma(32) and screened ORF overexpression libraries to identify sigma(32) inducers. We triple the number of genes validated to be transcribed by sigma(32). and provide new insights into the cellular role of this response. Our work indicates that the response is propagated as the regulon encodes numerous global transcriptional regulators, reveals that sigma(70) holoenzyme initiates from 12% of sigma(32) promoters, which has important implications for global transcriptional wiring, and identifies a new role for the response in protein homeostasis, that of protecting complex proteins. Finally, this study suggests that the response protects the cell membrane and responds to its status: Fully 25% of sigma(32) regulon members reside in the membrane and alter its functionality; moreover, a disproportionate fraction of overexpressed proteins that induce the response are membrane localized. The intimate connection of the response to the membrane rationalizes why a major regulator of the response resides in that cellular compartment.