Monteverde Ceschin, Robin
(2013)
Analysis of the Regulation of the S. Cerevisiae Gene PIR3 by Non-coding Intergenic Transcription.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Genome-wide studies have identified pervasive noncoding transcription across prokaryotic and eukaryotic genomes. Although many of these noncoding RNAs (ncRNAs) are likely the result of transcriptional noise, important regulatory functions have been elucidated for some of these transcripts. Previous studies in our lab have elucidated a regulatory mechanism in which transcription of the noncoding RNA, SRG1, regulates expression of the adjacent gene SER3 by directing nucleosome occupancy across the SER3 promoter, thereby blocking access of activators that induce transcription. A significant portion of noncoding transcription near promoters of protein-coding genes suggests a possible role in the regulation of transcription and initiation of these genes. In this investigation, I describe the identification of a new site of gene regulation by intergenic transcription at Saccharomyce cerevisiaePIR3 (Proteins with Internal Repeats 3), a gene encoding a cell wall protein identified from RNA pol II genome-wide data. I use a new method of disrupting transcription to assess the effect that loss of intergenic transcription has on PIR3 expression. This led to the identification of a repressive function for intergenic transcription in cis at PIR3.
Regulatory functions by ncRNAs have implications in human disease and development, which is often the result of epigenetic changes leading to altered chromatin states. Particu- larly, investigations of gene expression related to various cancers have provided examples of ncRNAs that can be used as biomarkers in predicting the likelihood of metastasis and silence tumor suppressor genes through epigenetic modifications. From a public health standpoint, studying the mechanisms by which ncRNAs regulate gene expression or the manner in which
3
epigenetic misregulation leads to disease will allow for more targeted therapies. Additionally, identification of ncRNA is useful in itself as a source of biomarkers in cancer and genetic diseases. This study has additional importance for the development of improved antifun- gals in the fight against resistant pathogenic strains of yeast, an increasing public health problem, particularly among immunocompromised patients. S. cerevisiae is a good model for pathogenic strains of yeast in terms of studying genes and proteins involved in cell wall regulation and biosynthesis which could aid in identifying effective therapies.
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Details
Item Type: |
University of Pittsburgh ETD
|
Status: |
Unpublished |
Creators/Authors: |
|
ETD Committee: |
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Date: |
29 January 2013 |
Date Type: |
Publication |
Defense Date: |
16 November 2012 |
Approval Date: |
29 January 2013 |
Submission Date: |
26 November 2012 |
Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
Number of Pages: |
79 |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
Degree: |
MS - Master of Science |
Thesis Type: |
Master's Thesis |
Refereed: |
Yes |
Uncontrolled Keywords: |
Transcription termination
cell wall
cis/trans |
Date Deposited: |
29 Jan 2013 22:02 |
Last Modified: |
15 Nov 2016 14:08 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/16930 |
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Analysis of the Regulation of the S. Cerevisiae Gene PIR3 by Non-coding Intergenic Transcription. (deposited 29 Jan 2013 22:02)
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