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

Soo Jeong Kyeong, Yang Xie, Hiroshi Hiasa, Arkady B. Khodursky

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPLoS Genetics
Volume2
Issue number9
DOIs
StatePublished - Sep 29 2006

Fingerprint

DNA Gyrase
DNA topoisomerase (ATP-hydrolysing)
DNA replication
DNA Replication
case studies
DNA topoisomerase
DNA
Regulon
regulon
Type I DNA Topoisomerase
DNA repair
DNA Repair
Genes
Linear Models
genes
linear models
Maintenance
repair
Genome
Escherichia coli

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Analysis of pleiotropic transcriptional profiles : a case study of DNA gyrase inhibition. / Kyeong, Soo Jeong; Xie, Yang; Hiasa, Hiroshi; Khodursky, Arkady B.

In: PLoS Genetics, Vol. 2, No. 9, 29.09.2006.

Research output: Contribution to journalArticle

Kyeong, Soo Jeong ; Xie, Yang ; Hiasa, Hiroshi ; Khodursky, Arkady B. / Analysis of pleiotropic transcriptional profiles : a case study of DNA gyrase inhibition. In: PLoS Genetics. 2006 ; Vol. 2, No. 9.
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