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The Effects of Chromatin Organization on Nuclear Mechanics and Chromatin Dynamics

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서명/저자사항The Effects of Chromatin Organization on Nuclear Mechanics and Chromatin Dynamics.
개인저자Johnston, Jessica Faith.
단체저자명Yale University. Cell Biology in MD/PhD Program.
발행사항[S.l.]: Yale University., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항177 p.
기본자료 저록Dissertations Abstracts International 81-03B.
Dissertation Abstract International
ISBN9781085776745
학위논문주기Thesis (Ph.D.)--Yale University, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: King, Megan C.
이용제한사항This item must not be sold to any third party vendors.
요약The cell nucleus houses the genome, which is compacted with a multi-level, complex organization ranging from single nucleosomes to entire chromosome territories. The predominant perspective of genome organization has focused on its gene expression effects, but an emerging area of study is uncovering the mechanical and dynamic effects of chromatin organization. Though much work has been done to characterize the composition of chromatin organization, the functionality of this organization is still under active investigation. Through the use of unique biophysical experimental and image analysis techniques, I here show that loss of specific epigenetic modifications has significant effects on the mechanics of the nucleus, further confirming an important non-genetic function of the genome in cell homeostasis. Specifically, my results highlight the mechanical contribution of Swi6, a heterochromatin protein (HP1) ortholog recently seen to form phase-separated domains. In addition, I demonstrate the contribution to chromatin dynamics of specific molecular players implicated in chromatin domain formation, forming a link between higher-order organization and chromatin dynamics. My results show that the SMC protein condensin, important for the formation and maintenance of topological associating domains, works to constrain chromatin mobility, while the actions of RNA polymerase enhance chromatin mobility. I anticipate this work to motivate further investigations into the mechanical and dynamic effects of chromatin, specifically how altered chromatin organization in diseases such as cancer could promote mechanical and dynamic states that feed forward mutagenesis and malignancy.
일반주제명Biophysics.
Cellular biology.
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