Upadhyai, Priyanka
(2013)
Unraveling Mechanisms of Transcriptional Repression: Novel Insights from Brinker.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Transcriptional repressors bind cis-regulatory elements of target genes in a sequence specific manner. To antagonize transcription, repressors primarily function by recruiting accessory proteins, co-repressors, which in turn largely function by modifying chromatin structure. Although a repressor could function by recruiting just a single co-repressor, many recruit more than one, with Brinker (Brk) from Drosophila recruiting the co-repressors, CtBP and Groucho (Gro), in addition to possessing a third repression domain, 3R. Previous studies indicated that Gro is sufficient for Brk to repress target genes in the wing imaginal disc, questioning why it should need to recruit CtBP, a ’short-range’ co-repressor compared to Gro that can function over longer distances. To resolve this I have used genomic engineering to generate a series of endogenous brk mutants that are unable to recruit Gro, CtBP and/or have the 3R domain deleted. Analysis of these mutants reveals that while the recruitment of Gro is necessary and is almost sufficient for Brk to make a morphologically wild-type fly, it is insufficient during oogenesis where Brk must utilize CtBP and 3R to pattern the egg-shell appropriately. Gro insufficiency during oogenesis can be explained by its downregulation in Brk-expressing cells through phosphorylation downstream of EGFR signaling, thus making it unavailable for Brk which must then resort to CtBP and/or 3R for repressive activity. The present study dissects the mechanism of activity of a transcription factor and its co-repressors and is the first to do so in multicellular eukaryotes in a physiologically relevant manner; additionally its findings provide a better understanding of why transcription factors in general may utilize more than one co-repressor.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Upadhyai, Priyanka | pru2@pitt.edu | PRU2 | |
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| ETD Committee: |
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| Date: |
30 September 2013 |
| Date Type: |
Publication |
| Defense Date: |
29 May 2013 |
| Approval Date: |
30 September 2013 |
| Submission Date: |
16 July 2013 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
173 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
repression, co-repressor, Brinker, Groucho |
| Date Deposited: |
30 Sep 2013 21:08 |
| Last Modified: |
15 Nov 2016 14:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19334 |
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