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Mutational Analysis of Xist and the X-inactivation Center
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Mutational Analysis of Xist and the X-inactivation Center. |
| 개인저자 | Goodrich, Leeanne. |
| 단체저자명 | University of California, San Francisco. Genetics. |
| 발행사항 | [S.l.]: University of California, San Francisco., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 88 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781687955197 |
| 학위논문주기 | Thesis (Ph.D.)--University of California, San Francisco, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Panning, Barbara. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | In placental mammals, dosage compensation of the sex chromosomes is achieved through inactivation of one X chromosome in female cells. This X chromosome inactivation (XCI) requires tight developmental regulation to ensure all but one X chromosome is silenced.At the center of this process is Xist, a long non-coding RNA. Upon differentiation of a female cell, Xist spreads in cis to coat and silence the inactive X chromosome. While upregulation of Xist, has been shown to be sufficient for X inactivation to occur, no one has thoroughly investigated whether Xist is necessary for the establishment of X chromosome inactivation. In this thesis I provide evidence that Xist is not required for dosage compensation of the X chromosome during epiblast-like cell differentiation. This result suggests Xist-independent silencing mechanisms for this essential process may be in place.A 1-2 Mb region of the X chromosome, termed the X-inactivation center (Xic) is necessary in two copies for XCI to occur, indicating it is necessary for cells to count the number of X chromosomes present. I delete one copy of the putative 2 Mb Xic in male and female mouse embryonic stem cells and present evidence that this deletion is not well tolerated, suggesting that this region requires finer resolution mapping to identify the minimal element required for counting.Finally, I finish with a review which elaborates on studies that enlighten our understanding of activators and repressors that control XCI. Our findings challenge existing dogmas in the field and provide the foundation for future work focused on uncovering the molecular mechanisms behind Xist-independent silencing of the X chromosome. |
| 일반주제명 | Genetics. Molecular biology. Developmental biology. |
| 언어 | 영어 |
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