rapid changes in gene expression dynamics in response to superoxide reveal soxrs-dependent and independent transcriptional networks基因表达的快速变化动力学响应超氧化物揭示soxrs-dependent和独立的转录网络.pdfVIP

Rapid Changes in Gene Expression Dynamics in Response to Superoxide Reveal SoxRS-Dependent and Independent Transcriptional Networks 1 1¤ 2 1 Jeffrey L. Blanchard *, Wei-Yun Wholey , Erin M. Conlon , Pablo J. Pomposiello 1 Department of Microbiology, University of Massachusetts, Amherst, Massachusetts, United States of America, 2 Department of Mathematics and Statistics, University of Massachusetts, Amherst, Massachusetts, United States of America Background. SoxR and SoxS constitute an intracellular signal response system that rapidly detects changes in superoxide levels and modulates gene expression in E. coli. A time series microarray design was used to identify co-regulated SoxRS- dependent and independent genes modulated by superoxide minutes after exposure to stress. Methodology/Principal Findings. soxS mRNA levels surged to near maximal levels within the first few minutes of exposure to paraquat, a superoxide- producing compound, followed by a rise in mRNA levels of known SoxS-regulated genes. Based on a new method for determining the biological significance of clustering results, a total of 138 genic regions, including several transcription factors and putative sRNAs were identified as being regulated through the SoxRS signaling pathway within 10 minutes of paraquat treatment. A statistically significant two-block SoxS motif was identified through analysis of the SoxS-regulated genes. The SoxRS-independent response included members of the OxyR, CysB, IscR, BirA and Fur regulons. Finally, the relative sensitivity to superoxide was measured in 94 strains carrying deletions in individual, superoxide-regulated genes. Conclusions/ Significance. By integrating our microarray time series results with other microarray data, E. coli databases and the pri