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Polycomb Silencing of the Thor Gene

Mason-Suares, Heather Marie
http://rave.ohiolink.edu/etdc/view?acc_num=case1277323215

Abstract Details

2010, Doctor of Philosophy, Case Western Reserve University, Genetics.
In addition to their well-known role in epigenetic silencing of the homeotic genes, Polycomb group (PcG) proteins have been implicated in a growing number of developmental processes. Homozygous mutations in the Polycomb Repressive Complex 2 (PRC2) subunits E(Z), SU(Z)12, or both ESC and ESCL cause an imaginal disc growth defect. They survive through the larval period, due to maternal rescue, but have small imaginal discs that are unable to develop into adult structures, resulting in a failure to pupate. Here we report that E(z) homozygotes also exhibit a cell growth defect; the cells comprising their small imaginal discs are also smaller than normal. To identify potential direct targets of Polycomb silencing that might underlie the small disc phenotype; we searched a list of candidate genes for binding sites for DNA binding proteins found in well-characterized Polycomb Response Elements (PREs). Using this approach, we identified a putative PRE in the Thor gene, which encodes the global translational inhibitor eI4E-Binding Protein (4E-BP). We confirmed that PcG proteins bind to the Thor gene by chromatin immuno-precipitation. We show that PRC2 homozygotes, but not heterozygotes, have elevated levels of 4E-BP. Deletion of the Thor gene is also able to partially restore wild-type disc size in E(z) homozygotes and promote advancement through pupariation, but not pupation. These data indicate that the Thor gene is a direct target of Polycomb silencing in imaginal discs and indicate that silencing of the Thor gene plays a role in promoting normal imaginal disc growth and the subsequent progression through pupariation. The transcription factor FOXO (Forkhead box, subgroup O) up-regulates the transcription of the Thor gene in response to nutritional stress. To determine how FOXO up-regulates Thor transcription when it is simultaneously inhibited by PcG proteins, we utilize serum-starved S2 cells. Serum starving S2 cells causes FOXO to translocate into the nucleus, bind to the Thor promoter and increase Thor transcription. Here we show that starvation displaces PcG proteins from the Thor promoter after 24 hours of starvation, however, the mechanism is still unknown.
Mitch Drumm, PhD (Committee Chair)
Peter Harte, PhD (Advisor)
Heather Broihier, PhD (Committee Member)
Kurt Runge, PhD (Committee Member)
Bruce Lamb, PhD (Committee Member)
189 p.
Genetics
Polycomb Silencing; Thor; 4E-BP; Enhancer of Zeste; Extra Sex Combs; Suppressor of Zeste12

Recommended Citations

Citations

  • Mason-Suares, H. M. (2010). Polycomb Silencing of the Thor Gene [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1277323215

    APA Style (7th edition)

  • Mason-Suares, Heather. Polycomb Silencing of the Thor Gene. 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1277323215.

    MLA Style (8th edition)

  • Mason-Suares, Heather. "Polycomb Silencing of the Thor Gene." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1277323215

    Chicago Manual of Style (17th edition)

case1277323215
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© 2010, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.