Home LiteratureArticle Details
PMID: 17009874 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

Analysis of pleiotropic transcriptional profiles: a case study of DNA gyrase inhibition.

PLoS genetics ·Vol. 2 ·No. 9 ·2006-09-29 ·Pages e152

Jeong KS, Xie Y, Hiasa H, Khodursky AB

Abstract

Genetic and environmental perturbations often result in complex transcriptional responses involving multiple genes and regulons. In order to understand the nature of a response, one has to account for the contribution of the downstream effects to the formation of a response. Such analysis can be carried out within a statistical framework in which the individual effects are independently collected and then combined within a linear model. Here, we modeled the contribution of DNA replication, supercoiling, and repair to the transcriptional response of inhibition of the Escherichia coli gyrase. By representing the gyrase inhibition as a true pleiotropic phenomenon, we were able to demonstrate that: (1) DNA replication is required for the formation of spatial transcriptional domains; (2) the transcriptional response to the gyrase inhibition is coordinated between at least two modules involved in DNA maintenance, relaxation and damage response; (3) the genes whose transcriptional response to the gyrase inhibition does not depend on the main relaxation activity of the cell can be classified on the basis of a GC excess in their upstream and coding sequences; and (4) relaxation by topoisomerase I dominates the transcriptional response, followed by the effects of replication and RecA. We functionally tested the effect of the interaction between relaxation and repair activities, and found support for the model derived from the microarray data. We conclude that modeling compound transcriptional profiles as a combination of downstream transcriptional effects allows for a more realistic, accurate, and meaningful representation of the transcriptional activity of a genome.

MeSH Terms
DNA Gyrase/physiology DNA Repair/physiology DNA Replication/physiology DNA Topoisomerases, Type I/physiology Escherichia coli/genetics Gene Expression Profiling/methods Gene Expression Regulation, Bacterial Molecular Sequence Data Organisms, Genetically Modified Rec A Recombinases/physiology Topoisomerase II Inhibitors Transcription, Genetic/physiology
Chemicals
Topoisomerase II Inhibitors Rec A Recombinases DNA Topoisomerases, Type I DNA Gyrase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jeong Kyeong Soo
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, St. Paul, Minnesota, United States of America.
Xie Yang
Hiasa Hiroshi
Khodursky Arkady B
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

References (69)
69 references, click to expand
  1. Complete enzymatic replication of plasmids containing the origin of the Escherichia coli chromosome.
    J Biol Chem. 1986 Apr 25;261(12):5616-24 PMID: 3514619
  2. Repetitive extragenic palindromic sequences: a major component of the bacterial genome.
    Cell. 1984 Jul;37(3):1015-26 PMID: 6378385
  3. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli.
    J Biol Chem. 2000 Mar 17;275(11):8103-13 PMID: 10713132
  4. Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling.
    Cell. 1983 Aug;34(1):105-13 PMID: 6309403
  5. Topological domain structure of the Escherichia coli chromosome.
    Genes Dev. 2004 Jul 15;18(14):1766-79 PMID: 15256503
  6. Replication arrests during a single round of replication of the Escherichia coli chromosome in the absence of DnaC activity.
    Mol Microbiol. 2001 Dec;42(5):1371-82 PMID: 11886566
  7. The SOS regulatory system of Escherichia coli.
    Cell. 1982 May;29(1):11-22 PMID: 7049397
  8. Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12.
    Antimicrob Agents Chemother. 1986 Aug;30(2):248-53 PMID: 3532944
  9. Mechanisms of quinolone resistance in a clinical isolate of Escherichia coli highly resistant to fluoroquinolones but susceptible to nalidixic acid.
    Antimicrob Agents Chemother. 1991 Mar;35(3):519-23 PMID: 2039202
  10. DNA gyrase-mediated wrapping of the DNA strand is required for the replication fork arrest by the DNA gyrase-quinolone-DNA ternary complex.
    J Biol Chem. 2000 Nov 3;275(44):34780-6 PMID: 11053451
  11. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli.
    Genetics. 2001 May;158(1):41-64 PMID: 11333217
  12. Histonelike proteins of bacteria.
    Microbiol Rev. 1987 Sep;51(3):301-19 PMID: 3118156
  13. Evidence for RecA protein association with the cell membrane and for changes in the levels of major outer membrane proteins in SOS-induced Escherichia coli cells.
    J Bacteriol. 1985 Sep;163(3):870-6 PMID: 3897198
  14. Different mechanisms of thioredoxin in its reduced and oxidized forms in defense against hydrogen peroxide in Escherichia coli.
    Free Radic Biol Med. 1998 Mar 1;24(4):556-62 PMID: 9559867
  15. DNA topoisomerases: structure, function, and mechanism.
    Annu Rev Biochem. 2001;70:369-413 PMID: 11395412
  16. Activation and silencing of leu-500 promoter by transcription-induced DNA supercoiling in the Salmonella chromosome.
    Mol Microbiol. 2000 Aug;37(3):583-94 PMID: 10931352
  17. Identification of additional genes belonging to the LexA regulon in Escherichia coli.
    Mol Microbiol. 2000 Mar;35(6):1560-72 PMID: 10760155
  18. Acetylornithinase of Escherichia coli: partial purification and some properties.
    J Biol Chem. 1956 Jan;218(1):97-106 PMID: 13278318
  19. RecA-dependent mutants in Escherichia coli reveal strategies to avoid chromosomal fragmentation.
    Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16262-7 PMID: 15531636
  20. Escherichia coli spotted double-strand DNA microarrays: RNA extraction, labeling, hybridization, quality control, and data management.
    Methods Mol Biol. 2003;224:61-78 PMID: 12710666
  21. Reinitiation of deoxyribonucleic acid synthesis by deoxyribonucleic acid initiation mutants of Escherichia coli: role of ribonucleic acid synthesis, protein synthesis, and cell division.
    J Bacteriol. 1975 Jan;121(1):219-26 PMID: 1090569
  22. A physiological role for DNA supercoiling in the osmotic regulation of gene expression in S. typhimurium and E. coli.
    Cell. 1988 Feb 26;52(4):569-84 PMID: 2830029
  23. BioProspector: discovering conserved DNA motifs in upstream regulatory regions of co-expressed genes.
    Pac Symp Biocomput. 2001;:127-38 PMID: 11262934
  24. Analysis of topoisomerase function in bacterial replication fork movement: use of DNA microarrays.
    Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9419-24 PMID: 10944214
  25. DNA gyrase on the bacterial chromosome. Oxolinic acid-induced DNA cleavage in the dnaA-gyrB region.
    J Mol Biol. 1988 May 5;201(1):229-33 PMID: 2843645
  26. Viability of Escherichia coli topA mutants lacking DNA topoisomerase I.
    J Biol Chem. 2005 Jan 7;280(1):355-60 PMID: 15522872
  27. Conformational and thermodynamic properties of supercoiled DNA.
    Annu Rev Biophys Biomol Struct. 1994;23:609-43 PMID: 7919794
  28. The mechanism of inhibition of topoisomerase IV by quinolone antibacterials.
    J Biol Chem. 1998 Oct 16;273(42):27668-77 PMID: 9765303
  29. Nature of the SOS-inducing signal in Escherichia coli. The involvement of DNA replication.
    J Mol Biol. 1990 Mar 5;212(1):79-96 PMID: 2108251
  30. A microarray-based antibiotic screen identifies a regulatory role for supercoiling in the osmotic stress response of Escherichia coli.
    Genome Res. 2003 Feb;13(2):206-15 PMID: 12566398
  31. Expression of the recA gene is reduced in Escherichia coli topoisomerase I mutants.
    Mutat Res. 1990 Apr;243(4):267-72 PMID: 2157980
  32. DNA supercoiling in vivo.
    Biophys Chem. 1988 Feb;29(1-2):7-15 PMID: 2833949
  33. Transcription generates positively and negatively supercoiled domains in the template.
    Cell. 1988 May 6;53(3):433-40 PMID: 2835168
  34. In vivo cleavage of Escherichia coli BIME-2 repeats by DNA gyrase: genetic characterization of the target and identification of the cut site.
    Mol Microbiol. 1997 Nov;26(4):767-77 PMID: 9427406
  35. Lethal action of quinolones against a temperature-sensitive dnaB replication mutant of Escherichia coli.
    Antimicrob Agents Chemother. 2006 Jan;50(1):362-4 PMID: 16377712
  36. Escherichia coli mutants with temperature-sensitive synthesis of DNA.
    Mol Gen Genet. 1970;109(2):107-22 PMID: 4925091
  37. Replication of superhelical DNAs in vitro.
    Prog Nucleic Acid Res Mol Biol. 1986;33:111-40 PMID: 3541040
  38. DNA gyrase, topoisomerase IV, and the 4-quinolones.
    Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92 PMID: 9293187
  39. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.
    Nucleic Acids Res. 2002 Feb 15;30(4):e15 PMID: 11842121
  40. Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli.
    Genome Biol. 2004;5(11):R87 PMID: 15535863
  41. Spatial patterns of transcriptional activity in the chromosome of Escherichia coli.
    Genome Biol. 2004;5(11):R86 PMID: 15535862
  42. Topological promoter coupling in Escherichia coli: delta topA-dependent activation of the leu-500 promoter on a plasmid.
    J Bacteriol. 1994 Jun;176(12):3757-64 PMID: 8206854
  43. Regional organization of gene expression in Streptomyces coelicolor.
    Gene. 2005 Jun 20;353(1):53-66 PMID: 15936160
  44. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression.
    Nat Genet. 2000 Oct;26(2):183-6 PMID: 11017073
  45. Tus-mediated arrest of DNA replication in Escherichia coli is modulated by DNA supercoiling.
    Mol Microbiol. 2005 Nov;58(3):758-73 PMID: 16238625
  46. Need for DNA topoisomerase activity as a swivel for DNA replication for transcription of ribosomal RNA.
    Nature. 1987 Mar 26-Apr 1;326(6111):414-6 PMID: 2436053
  47. Osmotic regulation of porin expression: a role for DNA supercoiling.
    Mol Microbiol. 1989 Sep;3(9):1287-94 PMID: 2552265
  48. The expression of Escherichia coli SOS genes recA and uvrA is inducible by polyamines.
    Biochem Biophys Res Commun. 1999 Oct 22;264(2):584-9 PMID: 10529406
  49. Characterization of dnaC2 and dnaC28 mutants by flow cytometry.
    J Bacteriol. 1998 Apr;180(7):1624-31 PMID: 9537356
  50. Influence of DNA topology on expression of the tdc operon in Escherichia coli K-12.
    Mol Gen Genet. 1995 Jun 25;247(6):764-7 PMID: 7616969
  51. DNA gyrase binds to the family of prokaryotic repetitive extragenic palindromic sequences.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8850-4 PMID: 2848243
  52. Supercoiled DNA.
    Sci Am. 1980 Jul;243(1):100-13 PMID: 6256851
  53. SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis.
    Basic Life Sci. 1975;5A:355-67 PMID: 1103845
  54. DNA supercoiling and the anaerobic and growth phase regulation of tonB gene expression.
    J Bacteriol. 1988 Jun;170(6):2816-26 PMID: 2836373
  55. Topological unwinding of strong and weak promoters by RNA polymerase. A comparison between the lac wild-type and the UV5 sites of Escherichia coli.
    J Mol Biol. 1987 Jun 20;195(4):795-808 PMID: 3309341
  56. Long-range interaction between two promoters: activation of the leu-500 promoter by a distant upstream promoter.
    Cell. 1995 Aug 11;82(3):445-51 PMID: 7634334
  57. Topoisomerase IV is a target of quinolones in Escherichia coli.
    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11801-5 PMID: 8524852
  58. Bacterial chromosome segregation: evidence for DNA gyrase involvement in decatenation.
    Cell. 1984 Apr;36(4):1081-8 PMID: 6323018
  59. Escherichia coli DNA topoisomerase I inhibits R-loop formation by relaxing transcription-induced negative supercoiling.
    J Biol Chem. 1999 Jun 4;274(23):16659-64 PMID: 10347234
  60. Significance analysis of microarrays applied to the ionizing radiation response.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21 PMID: 11309499
  61. DNA strand cleavage is required for replication fork arrest by a frozen topoisomerase-quinolone-DNA ternary complex.
    J Biol Chem. 1996 Oct 18;271(42):26424-9 PMID: 8824300
  62. Application of false discovery rate procedure to pairwise comparisons of refractive index of glass fragments.
    Forensic Sci Int. 2006 Jun 27;160(1):53-8 PMID: 16221535
  63. Statistical tests for differential expression in cDNA microarray experiments.
    Genome Biol. 2003;4(4):210 PMID: 12702200
  64. Structural and functional diversity among bacterial interspersed mosaic elements (BIMEs).
    Mol Microbiol. 1994 Apr;12(1):61-70 PMID: 8057840
  65. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 PMID: 10829079
  66. DNA gyrase: an enzyme that introduces superhelical turns into DNA.
    Proc Natl Acad Sci U S A. 1976 Nov;73(11):3872-6 PMID: 186775
  67. Identification of a potent decatenating enzyme from Escherichia coli.
    J Biol Chem. 1988 Sep 15;263(26):13366-73 PMID: 2843517
  68. Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9697-702 PMID: 12119387
  69. Transcription-induced barriers to supercoil diffusion in the Salmonella typhimurium chromosome.
    Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3398-403 PMID: 14993611
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0020152
Published
2006-09-29
Epub
2006-00-02
Pages
e152
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1584274
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066098 · United States
NIGMS NIH HHS · GM59465 · United States
NIGMS NIH HHS · GM66098 · United States
Databases
GEO
GSE4408
SWISSPROT
P00274, P00477, P00891, P02928, P02930, P02931, P02943, P03017, P03033, P04384, P04475, P04982, P05042, P06612, P06715, P06957, P07905, P08622, P08846, P09151, P10151, P10384, P10413, P11875, P14175, P14176, P14177, P14294, P15282, P16936, P20082, P20083, P21168, P23538, P24209, P25553, P27241, P29018, P30125, P30126, P30127, P33232, P36683, P37347, P45803, P75870
External Links
PubMed source DOI: 10.1371/journal.pgen.0020152 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2