A microarray-based antibiotic screen identifies a regulatory role for supercoiling in the osmotic stress response of Escherichia coli
A microarray-based antibiotic screen identifies a regulatory role for supercoiling in the osmotic stress response of Escherichia coli
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DOI：
10.1101/gr.401003
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发表时间：
2003-02-01
期刊：
影响因子：
7
通讯作者：
Church, GM
中科院分区：
文献类型：
--
作者：
Cheung, KJ;Badarinarayana, V;Church, GM
DNA 超螺旋的变化是由大肠杆菌中的多种环境应激引起的，但这些反应的生理意义仍不清楚。我们现在证明，负超螺旋的增加对于大量渗透应激反应基因的转录激活是必要的。使用基于微阵列的方法，我们结合微生物抗生素新生霉素、培氟沙星和氯霉素，通过高盐条件下的表达谱来表征超螺旋依赖性基因转录。用于测量细胞功能的算法聚类和统计测量表明，该子集富含在渗透保护剂运输/合成和 rpoS 驱动的固定相适应中关键的基因。转录因子结合位点分析也支持全局应激西格玛因子 rpoS 的调节。此外，这些研究还揭示了渗透应激调节子中 60 个未表征的基因，并为超螺旋在控制应激诱导的转录中发挥更广泛的作用提供了证据。
Changes in DNA supercoiling are induced by a wide range of environmental stresses in Escherichia coli, but the physiological significance of these responses remains unclear. We now demonstrate that an increase in negative supercoiling is necessary for transcriptional activation of a large subset of osmotic stress-response genes. Using a microarray-based approach, we have characterized supercoiling-dependent gene transcription by expression profiling under conditions of high salt, in conjunction with the microbial antibiotics novobiocin, pefloxacin, and chloramphenicol. Algorithmic clustering and statistical measures for gauging cellular function show that this subset is enriched for genes critical in osmoprotectant transport/synthesis and rpoS-driven stationary phase adaptation. Transcription factor binding site analysis also supports regulation by the global stress sigma factor rpoS. In addition, these studies implicate 60 uncharacterized genes in the osmotic stress regulon, and offer evidence for a broader role for supercoiling in the control of stress-induced transcription.