Cross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κ B-dependent genes regulated by TNFα and heat shock

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dc.citation.journalTitleMolecular Genetics and Genomicsen_US
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.date.accessioned2015-06-30T16:22:57Zen_US
dc.date.available2015-06-30T16:22:57Zen_US
dc.date.issued2015en_US
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.identifier.citationJanus, Patryk, Stokowy, Tomasz, Jaksik, Roman, et al.. "Cross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κ B-dependent genes regulated by TNFα and heat shock." <i>Molecular Genetics and Genomics,</i> (2015) Springer: http://dx.doi.org/10.1007/s00438-015-1055-1.en_US
dc.identifier.doihttp://dx.doi.org/10.1007/s00438-015-1055-1en_US
dc.identifier.urihttps://hdl.handle.net/1911/80839en_US
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordChIP-seqen_US
dc.subject.keywordHSF1en_US
dc.subject.keywordheat shocken_US
dc.subject.keywordmicroarraysen_US
dc.subject.keywordNF-?Ben_US
dc.subject.keywordtranscription factor bindingen_US
dc.titleCross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κ B-dependent genes regulated by TNFα and heat shocken_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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