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Mol Genet Genomics. 2015 Oct;290(5):1979-90. doi: 10.1007/s00438-015-1055-1. Epub 2015 May 6.

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

Author information

1
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
2
Institute of Automatic Control, Silesian University of Technology, Akademicka 16, Gliwice, Poland.
3
Faculty of Automatic Control, Electronics and Computer Sciences, Silesian University of Technology, Akademicka 16, Gliwice, Poland.
4
Department of Clinical Science, University of Bergen, Postboks 7804, Bergen, Norway.
5
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan, Poland.
6
Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, Poznan, Poland.
7
Department of Statistics, Rice University, 6100 Main Street, Houston, TX, USA.
8
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland. widlak@io.gliwice.pl.

Abstract

Heat 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.

KEYWORDS:

ChIP-seq; HSF1; Heat shock; Microarrays; NF-κB; Transcription factor binding

PMID:
25944781
PMCID:
PMC4768219
DOI:
10.1007/s00438-015-1055-1
[Indexed for MEDLINE]
Free PMC Article

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