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020 ▼a 9781085776745
035 ▼a (MiAaPQ)AAI13807199
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 574
1001 ▼a Johnston, Jessica Faith.
24514 ▼a The Effects of Chromatin Organization on Nuclear Mechanics and Chromatin Dynamics.
260 ▼a [S.l.]: ▼b Yale University., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 177 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
500 ▼a Advisor: King, Megan C.
5021 ▼a Thesis (Ph.D.)--Yale University, 2019.
506 ▼a This item must not be sold to any third party vendors.
520 ▼a The 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.
590 ▼a School code: 0265.
650 4 ▼a Biophysics.
650 4 ▼a Cellular biology.
690 ▼a 0786
690 ▼a 0379
71020 ▼a Yale University. ▼b Cell Biology in MD/PhD Program.
7730 ▼t Dissertations Abstracts International ▼g 81-03B.
773 ▼t Dissertation Abstract International
790 ▼a 0265
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490495 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK