Library

eCommons

 

Uncovering prominent gene regulatory strategies through rate-limiting steps in transcription

Simple item page
dc.contributor.authorDeBerardine, Michael
dc.contributor.chairLis, Johnen_US
dc.contributor.committeeMemberDanko, Charlesen_US
dc.contributor.committeeMemberYu, Haiyuanen_US
dc.contributor.committeeMemberGrimson, Andrewen_US
dc.date.accessioned2024-01-31T21:18:46Z
dc.date.issued2023-05
dc.description.abstractWhile many factors are involved in the regulation of gene transcription, each of these must ultimately act to affect the rate at which RNA Polymerase II (Pol II) transcribes a given gene. As this rate is determined at one or more rate-limiting steps in transcription, we expect that a wide array of upstream regulatory process converge at these steps in order to modulate transcription of their target genes. I focus on two putative rate-determining steps present in higher eukaryotes: the processes preceding and including the initiation of gene transcription, including the recruitment of Pol II to gene promoters, and the release of paused Pol II from the promoter-proximal region into the gene body where it can then mediate productive gene transcription. After a general introduction to Pol II pausing and a presentation of novel software I’ve written for studying transcription, the next major section of my dissertation focuses on the pausing factor NELF, which binds Pol II to induce pausing in higher eukaryotes. Using Drosophila melanogaster as a model system, I find that the presence of NELF significantly enhances the regulatory potential of the transcriptional kinase Cdk9 in higher eukaryotes by establishing an efficient system of gene regulation based around NELF and Cdk9. After additional ancillary findings concerning NELF and another factor DSIF in Drosophila, I present an innovative experimental approach for determining the rate-limiting step at individual genes across the human genome. Preliminary findings here show that I can identify distinct sets of genes that are subject to regulatory at distinct points in transcription, laying the groundwork for the discovery of specific upstream regulatory pathways acting at these two discrete rate-determining steps modulating gene expression.en_US
dc.identifier.doihttps://doi.org/10.7298/51v7-ph17
dc.identifier.otherDeBerardine_cornellgrad_0058_13482
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:13482
dc.identifier.urihttps://hdl.handle.net/1813/114016
dc.language.isoen
dc.subjectBRGenomicsen_US
dc.subjectNELFen_US
dc.subjectP-TEFben_US
dc.subjectPol IIen_US
dc.subjectPromoter-proximal pausingen_US
dc.subjectTranscriptionen_US
dc.titleUncovering prominent gene regulatory strategies through rate-limiting steps in transcriptionen_US
dc.typedissertation or thesisen_US
dcterms.licensehttps://hdl.handle.net/1813/59810.2
thesis.degree.disciplineGenetics, Genomics and Development
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Genetics, Genomics and Development

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
DeBerardine_cornellgrad_0058_13482.pdf
Size:
6.65 MB
Format:
Adobe Portable Document Format
Download

Collections

Cornell Theses and Dissertations