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dc.contributor.authorZhang, Yien
dc.contributor.authorHatch, Kim Aen
dc.contributor.authorWernisch, Lorenzen
dc.contributor.authorBacon, Joannaen
dc.date.accessioned2011-06-16T16:29:55Z
dc.date.available2011-06-16T16:29:55Z
dc.date.issued2008-02-22en
dc.identifier.citationBMC Genomics 2008, 9:87
dc.identifier.issn1471-2164
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/237985
dc.description.abstractAbstract Background Low oxygen availability has been shown previously to stimulate M. tuberculosis to establish non-replicative persistence in vitro. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition. The aim of this study was to determine whether the induction of the entire DosR regulon is triggered as a synchronous event or if induction can unfold as a cascade of events as the differential expression of subsets of genes is stimulated by different oxygen availabilities. Results A novel aspect of our work is the use of chemostat cultures of M. tuberculosis which allowed us to control environmental conditions very tightly. We exposed M. tuberculosis to a sudden drop in oxygen availability in chemostat culture and studied the transcriptional response of the organism during the transition from a high oxygen level (10% dissolved oxygen tension or DOT) to a low oxygen level (0.2% DOT) using DNA microarrays. We developed a Bayesian change point analysis method that enabled us to detect subtle shifts in the timing of gene induction. It results in probabilities of a change in gene expression at certain time points. A computational analysis of potential binding sites upstream of the DosR-controlled genes shows how the transcriptional responses of these genes are influenced by the affinity of these binding sites to DosR. Our study also indicates that a subgroup of DosR-controlled genes is regulated indirectly. Conclusion The majority of the dosR-dependent genes were up-regulated at 0.2% DOT, which confirms previous findings that these genes are triggered by hypoxic environments. However, our change point analysis also highlights genes which were up-regulated earlier at levels of about 8% DOT indicating that they respond to small fluctuations in oxygen availability. Our analysis shows that there are pairs of divergent genes where one gene in the pair is up-regulated before the other, presumably for a flexible response to a constantly changing environment in the host.
dc.languageEnglishen
dc.language.isoen
dc.titleA Bayesian Change point model for differential gene expression patterns of the DosR regulon of Mycobacterium tuberculosisen
dc.typeArticle
dc.date.updated2011-06-16T16:29:55Z
dc.description.versionRIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.en
dc.rights.holderZhang et al.; licensee BioMed Central Ltd.
prism.publicationDate2008en
dcterms.dateAccepted2008-02-22en
rioxxterms.versionofrecord10.1186/1471-2164-9-87en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2008-02-22en
dc.identifier.eissn1471-2164
rioxxterms.typeJournal Article/Reviewen


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