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 Genomics
dc.contributor.authorJanus, Patryk
dc.contributor.authorStokowy, Tomasz
dc.contributor.authorJaksik, Roman
dc.contributor.authorSzoltysek, Katarzyna
dc.contributor.authorHandschuh, Luiza
dc.contributor.authorPodkowinski, Jan
dc.contributor.authorWidlak, Wieslawa
dc.contributor.authorKimmel, Marek
dc.contributor.authorWidlak, Piotr
dc.date.accessioned2015-06-30T16:22:57Z
dc.date.available2015-06-30T16:22:57Z
dc.date.issued2015
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1007/s00438-015-1055-1
dc.identifier.urihttps://hdl.handle.net/1911/80839
dc.language.isoeng
dc.publisherSpringer
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordChIP-seq
dc.subject.keywordHSF1
dc.subject.keywordheat shock
dc.subject.keywordmicroarrays
dc.subject.keywordNF-?B
dc.subject.keywordtranscription factor binding
dc.titleCross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κ B-dependent genes regulated by TNFα and heat shock
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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