자료유형  

 학위논문

Control Number  

0017161774

International Standard Book Number  

9798382784991

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Oei, Theresa Ann.

Publication, Distribution, etc. (Imprint  

[S.l.] : Harvard University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

155 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Kingston, Robert E.

Dissertation Note  

Thesis (Ph.D.)--Harvard University, 2024.

Summary, Etc.  

요약Polycomb group (PcG) proteins are key developmental regulators involved in gene repression and the maintenance of cell identity. They are a dynamic part of facultative chromatin found clustered in the nucleus as Polycomb bodies. Canonical Polycomb Repressive Complex 1 (cPRC1) is hypothesized to facilitate the silencing of chromatin by compaction and phase separation. The CBX subunit recruits cPRC1 to chromatin and has been shown to contribute to PRC1 condensate formation. The goal of my thesis work was to characterize the phase separation of PRC1 driven by paralogs of the CBX family of proteins and to demonstrate the function of phase separation in PRC1 epigenetic regulation.In Chapter 1, I will introduce PRC1 and its role in gene repression and development. I will also introduce the concept of liquid liquid phase separation and its proposed role in transcriptional control. Additionally, I will describe the many ways in which PcG proteins, such as the CBXs, are misregulated in cancer.In Chapter 2, I will describe my characterization of the CBX4 and CBX8 proteins and their phase separation activity both in vitro and in cells. I will show how positively charged amino acids in the intrinsically disordered regions of these proteins contribute to their condensate behavior and compare the dynamics of CBX4 and CBX8 to CBX2 in cells.In Chapter 3, I will share an adaptation of my submitted manuscript demonstrating that heterologous phase separation can rescue PRC1 function of a CBX2 phase separation mutant in a cancer model system.In Chapter 4, I will summarize the conclusions from my thesis research and discuss the ways in which this work advances the field of epigenetic regulation. I will also explore potential future directions for further understanding the mechanisms of CBX phase separation in Polycomb-mediated gene repression.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Oncology.

Index Term-Uncontrolled  

Condensates

Index Term-Uncontrolled  

Epigenetics

Index Term-Uncontrolled  

Phase separation

Index Term-Uncontrolled  

Polycomb group

Index Term-Uncontrolled  

Cancer

Added Entry-Corporate Name  

Harvard University Chemical Biology

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

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Control Number  

joongbu:656838