Modeling Nucleosomal DNA in Living Yeast Public Deposited

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  • March 20, 2019
Creator
  • Hult, Caitlin
    • Affiliation: College of Arts and Sciences, Department of Mathematics
Abstract
  • The genome in living yeast cells is a highly dynamic system where entropic interactions and nuclear confinement drive the formation of domains of high chromosomal interaction, known as topologically associating domains. We investigate dynamic organization and territory formation of 16 chromosomes in living yeast cells during interphase, using coarse-grained, entropic polymer chain models. We are interested in determining the mechanisms, such as packaging molecules that create loops within chromatin fibers, that govern inter- and intra-chromatin fluctuations and induce global features of the entire genome as well as more localized features of the nucleolus. The Bloom Lab measures specific DNA sites in specific chromosomes using live cell fluorescence microscopy. Our goal is to identify the sufficient biological and biophysical assumptions necessary to reproduce the experimental data, from which we aim to shed insights into dynamics and structure that are beyond current experimental resolution. In this dissertation, we show through a reductionist 3D mathematical model that entropic interactions are the driving mechanisms of the formation of domains of high chromosomal interaction and that enzymatic processes modulate the spatiotemporal dynamics of these domains. We present novel modeling and visualization techniques for nucleolus spatiotemporal dynamics. We explore the minimal physical requirements to segregate this region of repeated DNA from the rest of the genome, with a particular emphasis on the role of transient loop formation. Our findings support and significantly expand upon previous work.
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Rights statement
  • In Copyright
Advisor
  • Forest, Mark
  • Bloom, Kerry
  • Adalsteinsson, David
  • Griffith, Boyce
  • Vasquez, Paula
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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