Graduate Thesis Or Dissertation
Identification and Characterization of Functional Regulatory Variants in S. cerevisiae Público Deposited
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https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/6q182k231
- Abstract
- Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the need to define the mechanisms that control differences in gene expression regulation between individuals. I discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of S.cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, I identified a trans-acting single nucleotide polymorphism within the transcr¬iption factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that deletion of RIM101 in both backgrounds abrogated the majority of differential expression between S288c and ∑1278b and showed that RIM101 regulates many more targets in S288c than in ∑1278b. However, expression profiling of both strains harboring either RIM101 allele revealed that only three transcripts undergo a significant allele-dependent change in expression. Strikingly, hundreds of RIM101-dependent targets underwent a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. I conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.
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- Date Issued
- 2015
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- Última modificación
- 2019-11-16
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- Declaración de derechos
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Miniatura | Título | Fecha de subida | Visibilidad | Acciones |
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identificationAndCharacterizationOfFunctionalRegulatoryVari.pdf | 2019-11-13 | Público | Descargar |