• Nucleic acids research · Sep 2017

    Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells.

    • Catherine Rhee, Bum-Kyu Lee, Samuel Beck, Lucy LeBlanc, Haley O Tucker, and Jonghwan Kim.
    • Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
    • Nucleic Acids Res. 2017 Sep 29; 45 (17): 10103-10114.

    AbstractDirect reprogramming can be achieved by forced expression of master transcription factors. Yet how such factors mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Through embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS cell-specific 'CAG' factors (Cdx2, Arid3a and Gata3), we interrogate their chromosomal target occupancies, modulation of global transcription and chromatin accessibility at the initial stage of reprogramming. From the studies, we uncover a sequential, two-step mechanism of cellular reprogramming in which repression of pre-existing ES cell-associated gene expression program is followed by activation of TS cell-specific genes by CAG factors. Therefore, we reveal that CAG factors function as both decommission and pioneer factors during ES to TS-like cell fate conversion.© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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