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National University of Ireland – Galway

1. Carty, Ben. Epigenetic regulation of germline stem cell fate by Centromere Protein C .

Degree: 2021, National University of Ireland – Galway

Germline stem cells (GSCs) divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The ‘silent sister hypothesis’ proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate selective sister chromatid segregation in stem cells, this hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila GSCs, it has recently been shown that the centromeric histone CENP-A - the epigenetic determinant of centromere identity - is asymmetrically distributed on sister chromatids. In these cells, CENP-A deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. In this thesis, we report that the inner kinetochore protein CENP-C, which binds to centromeric chromatin, is required for the assembly of CENP-A in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CENP-A between stem and daughter cells. In addition, we show that CENP-A is gradually lost at the centromere of GSCs over time, with depletion of CENP-C accelerating this loss of CENP-A. Finally, we show that disruption to the centromeric core in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required for efficient asymmetric division in female Drosophila GSCs. Advisors/Committee Members: Dunleavy, Elaine (advisor).

Subjects/Keywords: Stem cells; Asymmetric Cell Division; Germline stem cell; Epigenetics; Centromere; Chromosome; CENP-C; CENP-A; Natural Sciences; Biochemistry; Science and Engineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Carty, B. (2021). Epigenetic regulation of germline stem cell fate by Centromere Protein C . (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/16500

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Carty, Ben. “Epigenetic regulation of germline stem cell fate by Centromere Protein C .” 2021. Thesis, National University of Ireland – Galway. Accessed March 01, 2021. http://hdl.handle.net/10379/16500.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Carty, Ben. “Epigenetic regulation of germline stem cell fate by Centromere Protein C .” 2021. Web. 01 Mar 2021.

Vancouver:

Carty B. Epigenetic regulation of germline stem cell fate by Centromere Protein C . [Internet] [Thesis]. National University of Ireland – Galway; 2021. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10379/16500.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carty B. Epigenetic regulation of germline stem cell fate by Centromere Protein C . [Thesis]. National University of Ireland – Galway; 2021. Available from: http://hdl.handle.net/10379/16500

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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