Degree Type

Thesis

Date of Award

2020

Degree Name

Master of Science

Department

Biochemistry, Biophysics and Molecular Biology

Major

Biochemistry

First Advisor

Davit A Potoyan

Abstract

Liquid-liquid phase separation of intrinsically disordered proteins has recently become a foundational mechanism in molecular and cell biology. The emergent ``liquid view" is offering a fresh perspective for understanding a longstanding problem of chromatin organization and regulation in eukaryotic nuclei. The family of heterochromatin proteins have been shown to undergo phase separation {in vivo} and {in vitro}, thereby providing clues for connecting molecular interactions of proteins, formation of heterochromatin domains, and the emergent gene regulatory processes. Understanding the molecular specificity and mechanisms by which heterochromatin proteins orchestrate nuclear processes, however, is a highly non-trivial question because of the multi-scale nature of the system, spanning from individual molecular components to large-scale nuclear domains. In this thesis, we report first steps toward understanding the multi-scale picture of heterochromatin protein actions. By carrying out simulations of heterochromatin protein components with all-atom and coarse-grained modeling, we shed light on detailed molecular features which drive the formation of aggregates and condensates in the nucleus. The study provides a stepping stone towards understanding heterochromatin formation and gene silencing from a ground-up molecular perspective.

DOI

https://doi.org/10.31274/etd-20200902-108

Copyright Owner

Jazelli Lenae Mueterthies

Language

en

File Format

application/pdf

File Size

36 pages

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