RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation

dc.contributor.authorSzołtysek, Katarzynaen_US
dc.contributor.authorJanus, Patryken_US
dc.contributor.authorZając, Gracjanaen_US
dc.contributor.authorStokowy, Tomaszen_US
dc.contributor.authorWalaszczyk, Annaen_US
dc.contributor.authorWidłak, Wiesławaen_US
dc.contributor.authorWojtaś, Bartoszen_US
dc.contributor.authorGielniewski, Bartłomiejen_US
dc.contributor.authorCockell, Simonen_US
dc.contributor.authorPerkins, Neil Den_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorWidlak, Piotren_US
dc.date.accessioned2018-11-28T16:43:41Zen_US
dc.date.available2018-11-28T16:43:41Zen_US
dc.date.issued11/12/2018en_US
dc.date.updated2018-11-28T16:43:40Zen_US
dc.description.abstractAbstract Background The cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gene targets. Here we looked for novel genes potentially (co)regulated by p53 and NF-κB using integrative genomics screening in human osteosarcoma U2-OS cells irradiated with a high dose (4 and 10 Gy). Radiation-induced expression in cells with silenced TP53 or RELA (coding the p65 NF-κB subunit) genes was analyzed by RNA-Seq while radiation-enhanced binding of p53 and RelA in putative regulatory regions was analyzed by ChIP-Seq, then selected candidates were validated by qPCR. Results We identified a subset of radiation-modulated genes whose expression was affected by silencing of both TP53 and RELA, and a subset of radiation-upregulated genes where radiation stimulated binding of both p53 and RelA. For three genes, namely IL4I1, SERPINE1, and CDKN1A, an antagonistic effect of the TP53 and RELA silencing was consistent with radiation-enhanced binding of both p53 and RelA. This suggested the possibility of a direct antagonistic (co)regulation by both factors: activation by NF-κB and inhibition by p53 of IL4I1, and activation by p53 and inhibition by NF-κB of CDKN1A and SERPINE1. On the other hand, radiation-enhanced binding of both p53 and RelA was observed in a putative regulatory region of the RRAD gene whose expression was downregulated both by TP53 and RELA silencing, which suggested a possibility of direct (co)activation by both factors. Conclusions Four new candidates for genes directly co-regulated by NF-κB and p53 were revealed.en_US
dc.identifier.citationSzołtysek, Katarzyna, Janus, Patryk, Zając, Gracjana, et al.. "RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation." (2018) BioMed Central: https://doi.org/10.1186/s12864-018-5211-y.en_US
dc.identifier.doihttps://doi.org/10.1186/s12864-018-5211-yen_US
dc.identifier.urihttps://hdl.handle.net/1911/103425en_US
dc.language.isoengen_US
dc.publisherBioMed Centralen_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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.rights.holderThe Author(s).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleRRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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