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Analysis of the Regulation of the S. Cerevisiae Gene PIR3 by Non-coding Intergenic Transcription

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 (Unpublished)

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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
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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:
CreatorsEmailPitt UsernameORCID
Monteverde Ceschin, Robinrobin.monteverde@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberMartinson, Jeremy J.jmartins@pitt.eduJMARTINS
Thesis AdvisorMartens, Joseph A.martens@pitt.eduMARTENS
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: Graduate 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) [Currently Displayed]

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