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dc.contributor.author Alexeyenko, A
dc.contributor.author Wassenberg, DM
dc.contributor.author Lobenhofer, EK
dc.contributor.author Yen, J
dc.contributor.author Linney, E
dc.contributor.author Sonnhammer, ELL
dc.contributor.author Meyer, JN
dc.date.accessioned 2011-06-21T17:31:30Z
dc.date.issued 2010
dc.identifier.citation PloS one, 2010, 5 (5), pp. e10465 - ?
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10161/4537
dc.description.abstract BACKGROUND: In order to generate hypotheses regarding the mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) causes toxicity, we analyzed global gene expression changes in developing zebrafish embryos exposed to this potent toxicant in the context of a dynamic gene network. For this purpose, we also computationally inferred a zebrafish (Danio rerio) interactome based on orthologs and interaction data from other eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: Using novel computational tools to analyze this interactome, we distinguished between dioxin-dependent and dioxin-independent interactions between proteins, and tracked the temporal propagation of dioxin-dependent transcriptional changes from a few genes that were altered initially, to large groups of biologically coherent genes at later times. The most notable processes altered at later developmental stages were calcium and iron metabolism, embryonic morphogenesis including neuronal and retinal development, a variety of mitochondria-related functions, and generalized stress response (not including induction of antioxidant genes). Within the interactome, many of these responses were connected to cytochrome P4501A (cyp1a) as well as other genes that were dioxin-regulated one day after exposure. This suggests that cyp1a may play a key role initiating the toxic dysregulation of those processes, rather than serving simply as a passive marker of dioxin exposure, as suggested by earlier research. CONCLUSIONS/SIGNIFICANCE: Thus, a powerful microarray experiment coupled with a flexible interactome and multi-pronged interactome tools (which are now made publicly available for microarray analysis and related work) suggest the hypothesis that dioxin, best known in fish as a potent cardioteratogen, has many other targets. Many of these types of toxicity have been observed in mammalian species and are potentially caused by alterations to cyp1a.
dc.format.extent e10465 - ?
dc.language.iso en_US en_US
dc.relation.ispartof PloS one
dc.relation.isversionof 10.1371/journal.pone.0010465
dc.title Dynamic zebrafish interactome reveals transcriptional mechanisms of dioxin toxicity.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-5-5 en_US
duke.description.endpage e10465 en_US
duke.description.issue 5 en_US
duke.description.startpage e10465 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Nicholas School of the Environment
pubs.organisational-group /Duke/Nicholas School of the Environment/Environmental Sciences and Policy
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.volume 5

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