Date of Award
Fall 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Genetics
First Advisor
Wang, Siyuan
Abstract
3D genomics is a rapidly emerging field that seeks to understand the role of the three-dimensional organization of the genome in gene regulation, cellular function, and biological processes. Chromatin tracing has recently emerged as an image-based highly multiplexed fluorescent in-situ hybridization method to detect 3D genome architectures in various biological contexts. However, the regulation of 3D genomics remains less understood. Recent advances in CRISPR screening have enabled systematic identification of genetic perturbations critical to cellular phenotypes and diseases. Yet, the phenotype readouts provided by current CRISPR screens are limited to low content, posing challenges for detection of complex 3D genome architectures. The first work of this thesis combined chromatin tracing with pooled CRISPR screen to build a platform that systematically identifies regulators of 3D genome architectures and investigated the molecular mechanisms of selected candidates. The second work applied chromatin tracing to X chromosomes in human pluripotent stem cells and identified distinct chromatin conformations, shedding insights into the relationship between 3D genome organization and X chromosome inactivation. The last work presented ProbeDealer, a computational tool for probe design to facilitate the research and application of 3D genomics.
Recommended Citation
Yang, Bing, "Exploring 3D Genomics and its Regulation: Spatial CRISPR Screening Reveals Regulators of 3D Genome Architectures and Chromatin Tracing Unfolds X Chromosome Conformations in Human Pluripotent Stem Cells" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1176.
https://elischolar.library.yale.edu/gsas_dissertations/1176
