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    Identification of MALAT1 as a PRC2-Ezh1 Associated lncRNA Essential for Epigenetic Control of Skeletal Muscle Adaptation and Plasticity

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    Name:
    NadineHosny_PhD_Thesis-final-Archiving 2019-- (1).pdf
    Size:
    15.49Mb
    Format:
    PDF
    Embargo End Date:
    2021-08-31
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    Type
    Dissertation
    Authors
    El Said, Nadine H. cc
    Advisors
    Orlando, Valerio cc
    Committee members
    Frøkjær-Jensen, Christian cc
    Tester, Mark A. cc
    Rinn, John
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Date
    2019-08
    Embargo End Date
    2021-08-31
    Permanent link to this record
    http://hdl.handle.net/10754/656509
    
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    Show full item record
    Access Restrictions
    At the time of archiving, the student author of this dissertation opted to temporarily restrict access to it. The full text of this dissertation will become available to the public after the expiration of the embargo on 2021-08-31.
    Abstract
    Polycomb Proteins (PcG) are chromatin proteins that control the maintenance of “transcriptional memory” and cell identity by fixing the repressed state of developmentally regulated genes. This function has been linked to interaction with RNA moieties, in particular long non-coding RNAs (lncRNAs). However, specificity of PcG-RNA interactions has been controversial (Beltran et al., 2016; Chen Davidovich, Leon Zheng, Karen J. Goodrich, & Thomas R. Cech, 2013). In this study we took advantage of recent work published from our lab reporting about a novel and reversible mechanism regulating genome wide Ezh1-PRC2 activation in mouse skeletal muscle cells in response to atrophic stress (Bodega et al., 2017). Using this physiological, in vivo tool we could identify a functional dynamic crosstalk between Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and PRC2-Ezh1 complex. By combining immuno-fluorescence, biochemistry, epigenomics, ChIRP, DNA and RNA immunoprecipitation we identified a novel pathway in which Malat1 plays a role in compartmentalization, assembly and activity of PRC2 in chromatin, allowing epigenetic plastic response to atrophic stress and recovery. We conclude that Malat1 is an essential partner for PRC2-Ezh1 adaptive function in skeletal muscle cells.
    Citation
    El Said, N. H. (2019). Identification of MALAT1 as a PRC2-Ezh1 Associated lncRNA Essential for Epigenetic Control of Skeletal Muscle Adaptation and Plasticity. KAUST Research Repository. https://doi.org/10.25781/KAUST-QQWM1
    DOI
    10.25781/KAUST-QQWM1
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-QQWM1
    Scopus Count
    Collections
    Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Dissertations

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