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Title: Notch target gene regulation by chromatin associated factors and Ecdysone signalling
Author: Goodfellow, H. A. I.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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In this thesis I have identified several chromatin associated proteins and transcription factors that can regulate. Notch target gene expression and suggested models of how they may function during transcription regulation of the Notch pathway. First, I have shown that a Histone chaperone protein, Asf1, is involved in Notch target gene repression. Based on data that Asf1 recruited by binding to components of the Su(H) repressor complex and that Asf1 exists in a timer with Histone H3/H4, a model was formulated in which Asf1 brings Histone dimers to form new nucleosides on Notch target genes to aid in repression. Second, a screen for potential chromatin associated proteins involved in Notch signalling was performed. Several chromatin related genes were found to genetically interact with the Notch pathway. Four of the best candidate genes were studied further with direct effects on Notch target genes shown. One of these genes was taiman, the co-activator of the Ecdysone receptor, which is part of the steroid signalling pathway in Drosophila. Further work on taiman revealed it was expressed in the wing disc but its role in regulation of Notch remains unclear. Third, the role of Ecdysone signalling in Notch target gene regulation was investigated further. A series of in vivo experiments were performed where Ecdysone signalling levels were manipulated by altering the activity of the Ecdysone receptor. Changes in Ecdysone signalling were able to regulate the expression of three Notch target genes in two different tissues. For some genes a synergistic response in expression was observed when both Notch and Ecdysone pathway were activated. Furthermore, one of the primary Ecdysone targets, the Broad complex, was also shown to affect Notch target gene expression, leading to model where both the Ecdysone receptor and the Broad isoforms may co-operate on the promoters of Notch target genes to regulate their temporal expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available