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    Regulation of human trophoblast syncytialization by histone demethylase LSD1

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    Foster_ku_0099M_14945_DATA_1.pdf (1.549Mb)
    Issue Date
    2016-12-31
    Author
    Foster, Jessica Marie Milano
    Publisher
    University of Kansas
    Format
    47 pages
    Type
    Thesis
    Degree Level
    M.S.
    Discipline
    Pathology & Laboratory Medicine
    Rights
    Copyright held by the author.
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    Abstract
    A successful pregnancy is critically dependent upon proper placental development and function, beginning with differentiation of human trophoblast cells. At the final stage of trophoblast differentiation, the human placenta contains a cell population called syncytiotrophoblasts which provide the exchange surface between the mother and the fetus. However, molecular regulation of syncytiotrophoblast development is poorly understood. In this study, we explored the regulatory pathway of lysine-specific demethylase 1 (LSD1), in combination with transcription factor GATA2 and cellular signaling, in human trophoblast syncytialization. Using cell culture models, we show that LSD1 is important for human trophoblast syncytialization. Cellular signaling, such as the activation of protein kinase A, together with LSD1 contribute to the recruitment of GATA2 at the Syncytin-1 and Syncytin-2 loci. Loss of LSD1 in trophoblast cells impairs GATA2 function, histone modifications and RNA polymerase II recruitment at Syncytin-1 and -2 loci leading to their transcriptional repression and impaired syncytialization. In summary, our data reveals a regulatory pathway demonstrating that LSD1 is essential for human trophoblast syncytialization.
    URI
    http://hdl.handle.net/1808/24807
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    • Theses [3711]

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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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