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    Effects of repetitive DNA and epigenetics on human genome regulation

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    JJINGO-DISSERTATION-2013.pdf (9.222Mb)
    Date
    2013-07-02
    Author
    Jjingo, Daudi
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    Abstract
    The highly developed and specialized anatomical and physiological characteristics observed for eukaryotes in general and mammals in particular are underwritten by an elaborate and intricate process of genome regulation. This precise control of the location, timing and amplitude of gene expression is achieved by a variety of genetic and epigenetic tools and mechanisms. While several of these regulatory mechanisms have been extensively studied, our understanding of the complex and diverse associations between various epigenetic marks and genetic elements with genome regulatory systems has remained incomplete. However, the recent profound improvements in sequencing technologies have significantly improved the depth and breadth to which their functions and relationships can be understood. The objective of this thesis has been to apply bioinformatics, computational and statistical tools to analyze and interpret various recent high throughput datasets from a combination of Next generation sequencing and Chromatin immune precipitation (ChIP-seq) experiments. These datasets have been analyzed to further our understanding of the dynamics of gene regulation in humans, particularly as it relates to repetitive DNA, cis-regulation and DNA methylation. The thesis thus resides at the intersection of three major areas; transposable elements, cis-regulatory elements and epigenetics. It explores how those three aspects of regulation relate with gene expression and the functional implications of those interactions. From this analysis, the thesis provides new insights into; 1) the relationship between the transposable element environment of human genes and their expression, 2) the role of mammalian-wide interspersed repeats (MIRs) in the function of human enhancers and enhancement of tissue-specic functions, 3) the existence and function of composite cis-regulatory elements and 4) the dynamics and relationship between human gene-body DNA methylation and gene expression.
    URI
    http://hdl.handle.net/1853/49120
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    • Georgia Tech Theses and Dissertations [22398]
    • School of Biology Theses and Dissertations [410]

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