Roles of TBP N-Terminus in 3D Genome Organization and Gene Regulation
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Date
2024
Authors
Lee, Brittney
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Recent studies have underscored the pivotal roles of transcription factors, such as the TATA-box binding protein (TBP), in governing gene expression dynamics by regulating the transcription process from DNA to RNA. Particular attention has been drawn to the multifaceted functionalities of the TBP N-terminus in transcriptional control and the structural organization of the genome in three dimensions. Investigations, notably utilizing fission yeast models, have elucidated its participation in coordinating responses to stress, ensuring proper gene distribution during cell division, and facilitating the establishment of gene territories via phase separation phenomena. Manipulation of the TBP N-terminus has yielded valuable insights into its contributions to transcriptional activity, cellular homeostasis, and genomic architecture under stress conditions, offering pertinent implications for comprehending fundamental cellular processes and potential mechanisms of disease, such as cancer. This thesis demonstrates that alterations to the TBP N-terminus impair both cell growth, as evidenced by spot tests and doubling time assays, and the overall organization of DNA, as observed through microscopic examination of TBP-N terminal mutants under various culturing conditions. Leveraging next-generation sequencing (NGS) technology, I reveal a widespread dampening of gene expression in TBP N-terminal mutants, albeit with no significant alterations in protein binding distribution overall.
Based on these observations, I posit that the TBP N-terminus plays a pivotal role in facilitating appropriate stress responses in fission yeast cells, thereby ensuring the accurate segregation of transcribed genes alongside their expression levels and spatial localization within the genome.
Description
61 pages
Keywords
TBP, N-Terminus, Phase Separation, Gene Regulation, Fission Yeast