relation: http://d-scholarship-dev.library.pitt.edu/16930/
title: Analysis of the Regulation of the S. Cerevisiae Gene PIR3 by Non-coding Intergenic Transcription
creator: Monteverde Ceschin, Robin
description: 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.
date: 2013-01-29
type: University of Pittsburgh ETD
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/16930/1/Robin_Ceschin_Finale-1.pdf
identifier:   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)