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    Noncoding Elements: Evolution and Epigenetic Regulation

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    Thesis.pdf
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    8.118Mb
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    Description:
    Dissertation
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    Type
    Dissertation
    Authors
    Seridi, Loqmane cc
    Advisors
    Ravasi, Timothy cc
    Committee members
    Gao, Xin cc
    Orlando, Valerio cc
    Carnici, Piero
    Program
    Computer Science
    KAUST Department
    Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
    Date
    2016-03-09
    Embargo End Date
    2017-03-09
    Permanent link to this record
    http://hdl.handle.net/10754/603694
    
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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 became available to the public after the expiration of the embargo on 2017-03-09.
    Abstract
    When the human genome project was completed, it revealed a surprising result. 98% of the genome did not code for protein of which more than 50% are repeats— later known as ”Junk DNA”. However, comparative genomics unveiled that many noncoding elements are evolutionarily constrained; thus luckily to have a role in genome stability and regulation. Though, their exact functions remained largely unknown. Several large international consortia such as the Functional Annotation of Mammalian Genomes (FANTOM) and the Encyclopedia of DNA Elements (ENCODE) were set to understand the structure and the regulation of the genome. Specifically, these endeavors aim to measure and reveal the transcribed components and functional elements of the genome. One of the most the striking findings of these efforts is that most of the genome is transcribed, including non-conserved noncoding elements and repeat elements. Specifically, we investigated the evolution and epigenetic properties of noncoding elements. 1. We compared genomes of evolutionarily distant species and showed the ubiquity of constrained noncoding elements in metazoa. 2. By integrating multi-omic data (such as transcriptome, nucleosome profiling, histone modifications), I conducted a comprehensive analysis of epigenetic properties (chromatin states) of conserved noncoding elements in insects. We showed that those elements have distinct and protective sequence features, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. 3. I focused on the relationship between enhancers and repetitive elements. Using Cap Analysis of Gene Expression (CAGE) and RNASeq, I compiled a full catalog of active enhancers (a class of noncoding elements) during myogenesis of human primary cells of healthy donors and donors affected by Duchenne muscular dystrophy (DMD). Comparing the two time-courses, a significant change in the epigenetic landscape in DMD was observed that lead to global dysregulation of enhancers and associated repetitive elements.
    Citation
    Seridi, L. (2016). Noncoding Elements: Evolution and Epigenetic Regulation. KAUST Research Repository. https://doi.org/10.25781/KAUST-V431P
    DOI
    10.25781/KAUST-V431P
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-V431P
    Scopus Count
    Collections
    PhD Dissertations; Computer Science Program; Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division

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