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dc.contributor.authorJanus, Patryken_US
dc.contributor.authorStokowy, Tomaszen_US
dc.contributor.authorJaksik, Romanen_US
dc.contributor.authorSzoltysek, Katarzynaen_US
dc.contributor.authorHandschuh, Luizaen_US
dc.contributor.authorPodkowinski, Janen_US
dc.contributor.authorWidlak, Wieslawaen_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorWidlak, Piotren_US
dc.PublishedMolecular Genetics and Genomics 2015, 290(5):1979-1990eng
dc.description.abstractHeat shock inhibits NF-κB signaling, yet the knowledge about its influence on the regulation of NF-κB-dependent genes is limited. Using genomic approaches, i.e., expression microarrays and ChIP-Seq, we aimed to establish a global picture for heat shock-mediated impact on the expression of genes regulated by TNFα cytokine. We found that 193 genes changed expression in human U-2 osteosarcoma cells stimulated with cytokine (including 77 genes with the κB motif in the proximal promoters). A large overlap between sets of genes modulated by cytokine or by heat shock was revealed (86 genes were similarly affected by both stimuli). Binding sites for heat shock-induced HSF1 were detected in regulatory regions of 1/3 of these genes. Furthermore, pre-treatment with heat shock affected the expression of 2/3 of cytokine-modulated genes. In the largest subset of co-affected genes, heat shock suppressed the cytokine-mediated activation (antagonistic effect, 83 genes), which genes were associated with the canonical functions of NF-κB signaling. However, subsets of co-activated and co-repressed genes were also revealed. Importantly, pre-treatment with heat shock resulted in the suppression of NF-κB binding in the promoters of the cytokine-upregulated genes, either antagonized or co-activated by both stimuli. In conclusion, we confirmed that heat shock inhibited activation of genes involved in the classical cytokine-mediated functions of NF-κB. On the other hand, genes involved in transcription regulation were over-represented in the subset of genes upregulated by both stimuli. This suggests the replacement of NF-κB-mediated regulation by heat shock-mediated regulation in the latter subset of genes, which may contribute to the robust response of cells to both stress conditions.en_US
dc.rightsAttribution CC BYeng
dc.subjectHeat shockeng
dc.subjectTranscription factor bindingeng
dc.titleCross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κB-dependent genes regulated by TNFα and heat shocken_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2015 the authors
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714
dc.subject.nsiVDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714

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