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dc.contributor.authorGrimaldi, Giulia
dc.contributor.authorRajendra, S.
dc.contributor.authorMatthews, J.
dc.date.accessioned2021-02-11T15:13:24Z
dc.date.available2021-02-11T15:13:24Z
dc.date.issued2018-01
dc.identifier.citationGrimaldi G, Rajendra S and Matthews J (2018) The aryl hydrocarbon receptor regulates the expression of TIPARP and its cis long non-coding RNA, TIPARP-AS1. Biochemical and Biophysical Research Communications. 495(3): 2356-2362.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18337
dc.descriptionYesen_US
dc.description.abstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and member of the basic helix-loop-helix-PAS family. AHR is activated by numerous dietary and endogenous compounds that contribute to its regulation of genes in diverse signaling pathways including xenobiotic metabolism, vascular development, immune responses and cell cycle control. However, it is most widely studied for its role in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. The AHR target gene and mono-ADP-ribosyltransferase, TCDD-inducible poly-ADP-ribose polymerase (TIPARP), was recently shown to be part of a novel negative feedback loop regulating AHR activity through mono-ADP-ribosylation. However, the molecular characterization of how AHR regulates TIPARP remains elusive. Here we show that activated AHR is recruited to the TIPARP promoter, through its binding to two genomic regions that each contain multiple AHR response elements (AHREs), AHR regulates the expression of both TIPARP but also TIPARP-AS1, a long non-coding RNA (lncRNA) which lies upstream of TIPARP exon 1 and is expressed in the opposite orientation. Reporter gene and deletion studies showed that the distal AHRE cluster predominantly regulated TIPARP expression while the proximal cluster regulated TIPARP-AS1. Moreover, time course and promoter activity assays suggest that TIPARP and TIPARP-AS1 work in concert to regulate AHR signaling. Collectively, these data show an added level of complexity in the AHR signaling cascade which involves lncRNAs, whose functions remain poorly understood.en_US
dc.description.sponsorshipThis work was supported by Canadian Institutes of Health Research (CIHR) operating grants (MOP-494265 and MOP-125919), an unrestricted research grant from the Dow Chemical Company, and the Johan Throne Holst Foundation to J.M. G.G. was supported by European Union Seventh Framework Program (FP7-PEOPLE2013-COFUND) under the Grant Agreement n609020 - Scientia Fellowsen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.bbrc.2017.12.113en_US
dc.rights© 2018 The Authors. Published by Elsevier Inc. Reproduced in accordance with the publisher's self-archiving policy. This version is made available under the https://creativecommons.org/licenses/by-nc-nd/4.0/.en_US
dc.subject2,3,7,8-Tetrachlorodibenzo-p-dioxinen_US
dc.subjectTCDD-inducible poly-ADP-ribose polymeraseen_US
dc.subjectLong non-coding RNAen_US
dc.subjectAryl hydrocarbon receptoren_US
dc.titleThe aryl hydrocarbon receptor regulates the expression of TIPARP and its cis long non-coding RNA, TIPARP-AS1en_US
dc.status.refereedYesen_US
dc.date.Accepted2017-12-20
dc.date.application2017-12-21
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2021-02-11T15:13:48Z
dc.openaccess.statusGreenen_US


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