title: Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli.
abstract: BACKGROUND
  The chromosome of Escherichia coli is maintained in a negatively supercoiled state, and supercoiling levels are affected by growth phase and a variety of environmental stimuli. In turn, supercoiling influences local DNA structure and can affect gene expression. We used microarrays representing nearly the entire genome of Escherichia coli MG1655 to examine the dynamics of chromosome structure.
  
  
  RESULTS
  We measured the transcriptional response to a loss of supercoiling caused either by genetic impairment of a topoisomerase or addition of specific topoisomerase inhibitors during log-phase growth and identified genes whose changes are statistically significant. Transcription of 7% of the genome (306 genes) was rapidly and reproducibly affected by changes in the level of supercoiling; the expression of 106 genes increased upon chromosome relaxation and the expression of 200 decreased. These changes are most likely to be direct effects, as the kinetics of their induction or repression closely follow the kinetics of DNA relaxation in the cells. Unexpectedly, the genes induced by relaxation have a significantly enriched AT content in both upstream and coding regions.
  
  
  CONCLUSIONS
  The 306 supercoiling-sensitive genes are functionally diverse and widely dispersed throughout the chromosome. We propose that supercoiling acts as a second messenger that transmits information about the environment to many regulatory networks in the cell.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA. bpeter@mrc-lmb.cam.ac.uk
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Peter
authors.forename: Javier
authors.initials: J
authors.lastname: Arsuaga
authors.forename: Adam M
authors.initials: AM
authors.lastname: Breier
authors.forename: Arkady B
authors.initials: AB
authors.lastname: Khodursky
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Cozzarelli
mesh_terms: D001482:Base Composition / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics*; D018387:Codon, Initiator / Q000235:genetics; D003374:Coumarins / Q000494:pharmacology; D026942:DNA Topoisomerases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004269:DNA, Bacterial / Q000235:genetics; D004278:DNA, Superhelical / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048168:Escherichia coli K12 / Q000201:enzymology / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D005798:Genes, Bacterial / Q000235:genetics / Q000502:physiology; D007700:Kinetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009643:Norfloxacin / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D059003:Topoisomerase Inhibitors; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D018387:Codon, Initiator; D003374:Coumarins; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D059003:Topoisomerase Inhibitors; C030123:coumarin; D026942:DNA Topoisomerases; D009643:Norfloxacin