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    The aryl hydrocarbon receptor regulates the expression of TIPARP and its cis long non-coding RNA, TIPARP-AS1

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    Grimaldi_BBRC_Final.pdf (603.2Kb)
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    Publication date
    2018-01
    Author
    Grimaldi, Giulia
    Rajendra, S.
    Matthews, J.
    Keyword
    2,3,7,8-Tetrachlorodibenzo-p-dioxin
    TCDD-inducible poly-ADP-ribose polymerase
    Long non-coding RNA
    Aryl hydrocarbon receptor
    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/.
    Peer-Reviewed
    Yes
    Open Access status
    Green
    
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    Abstract
    The 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.
    URI
    http://hdl.handle.net/10454/18337
    Version
    Published version
    Citation
    Grimaldi 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.
    Link to publisher’s version
    https://doi.org/10.1016/j.bbrc.2017.12.113
    Type
    Article
    Collections
    Life Sciences Publications

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