Determining the Role of the Xist Non-coding RNA in Epigenetic Programming of X-chromosome Inactivation

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  • March 20, 2019
Creator
  • Williams, Lucy H.
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Repression of Xist RNA expression is considered a prerequisite to reversing X-chromosome inactivation (XCI) in the mouse inner cell mass (ICM), and reactivation of X-linked genes is thought to follow loss of Xist RNA coating and heterochromatic markers of inactivation, such as methylation of histone H3. I analyzed X-chromosome activity in developing ICMs and show reactivation of gene expression from the inactive-X initiates in the presence of Xist coating and H3K27me3. Furthermore, depletion of Xist RNA coating through forced upregulation of NANOG does not result in altered reactivation kinetics. Taken together, our observations suggest that in the ICM, X-linked gene transcription and Xist coating are uncoupled. These data fundamentally alter our perception of the reactivation process and support the existence of a mechanism to reactivate Xp-linked genes that operates independent of loss of Xist RNA and H3K27me3 from the inactive-X.
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Curriculum of Genetics and Molecular Biology."
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  • Magnuson, Terry
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  • Chapel Hill, NC
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  • Open access

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