Modeling Genome Organization in Eukaryotic and Prokaryotic Cells Using Folding Determinant Interactions

The three-dimensional organization of genomes is fundamental to gene regulation, DNA replication, and cell identity. A key challenge, however, lies in disentangling stochastic folding driven by polymer physics from specific interactions mediated by nuclear landmarks and regulatory factors. In this thesis, I develop polymer-based chain-growth Monte Carlo frameworks to investigate genome folding in both mammalian and bacterial systems. For mammalian cells, I model how lamina-associated domains (LADs) and specific fold interactions (SFIs) contribute to nuclear architecture. By contrasting random polymer ensembles with models incorporating sparse specific interactions, I demonstrate that LAD–lamina tethering and SFIs act in a complementary manner to reproduce Hi-C features, compartmentalization, and insulation scores, while also accounting for the structural heterogeneity observed in single-cell imaging. For Escherichia coli, I extend this approach to its circular chromosome by integrating Hi-C data. The analysis reveals how Ori/Ter asymmetry, macrodomains, and supercoiling-sensitive regions influence chromosome compaction and long-range contacts. Comparisons with experimental data confirm that a small subset of specific interactions, beyond random polymer effects, is sufficient to capture the observed organization at both the population and single-cell levels. Together, these studies establish a unified framework for dissecting genome folding across organisms. By isolating SFIs from background polymer constraints, this work demonstrates how nuclear landmarks and topological features synergize with physical principles to generate robust yet heterogeneous genome structures.

Author dc:creator

• Pourya Delafrouz (18833926)

• Engineering
• Biomedical

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451686.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451686