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Dissecting the regulation of entry into gametogenesis in budding yeast

Tam, Janis; (2020) Dissecting the regulation of entry into gametogenesis in budding yeast. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Cells fate choices are governed by a multitude of signalling pathways during development. Environmental and internal cues converge onto important developmental genes that control transcriptional networks and in turn dictate cell fate outcomes. In budding yeast Saccharomyces cerevisiae, nutrient and mating type signals regulate the expression of a developmental gene called IME1. Upon nutrient starvation, IME1 is expressed and diploid cells are induced to enter a conserved cell differentiation programme known as sporulation or gametogenesis. During sporulation, meiotic cell divisions take place to generate four haploid spores. How nutrient signals modulate the expression of IME1 was unknown. In this thesis, I demonstrate that nutrient signals regulate repression of IME1 transcription. Glucose and rich nutrients including nitrogen compounds control the binding of an array of at least nine sequence-specific transcription factors to the IME1 promoter. The transcription factors in turn recruit Tup1-Cyc8, a conserved transcriptional repressor complex to inhibit IME1 transcription. Importantly, Tup1-Cyc8 is heavily involved in the repression of IME1 transcription, given that IME1 is fully de-repressed when Tup1-Cyc8 is depleted. I find that three transcription factors, Yap6, Sok2, and Phd1, play significant roles in mediating Tup1-Cyc8 repression of the IME1 promoter. Remarkably, IME1 transcription is highly responsive to changes in nutrient availability. I show that the IME1 promoter is poised for activation under Tup1-Cyc8 repression. Furthermore, IME1 transcription is rapidly activated when Tup1-Cyc8 is lost. My findings present a model of how complex signals regulate developmental genes at the transcriptional level to control cell fate decisions in eukaryotes.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Dissecting the regulation of entry into gametogenesis in budding yeast
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10092132
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