Title: Spatial organization and dynamics of chromatin polymers in their native folding state
Abstract: The spatial organization and dynamics of chromatin polymers are crucial physical properties for gaining a comprehensive understanding of genetic functions and the complex network of the DNA and its associated proteins. To model the native state of the chromatin folded by active loop extrusion, we develop a mean-field-like theory that self-consistently recapitulates the distribution of associated motor protein and simultaneously reproduces the chromatin spatial conformation measured by Hi-C contact map. We show that the chromatin loop extrusion is the primary mechanism that governs its organization in yeasts and vertebrates. We also develop a theoretical framework based on the Rouse-model polymer to study the dynamics of chromatin with loops. By conducting simulations, we show that the loop extrusion restricts chromatin mobility instead of enhancing it. Our Rouse-model looped polymer framework and simulation method can also be used to estimate first-passage times of chromatin self-contact reactions, which are important for gene regulation and additional chromosomal processes.
Defense Committee: Simon Mochrie (advisor), Megan King, Benjamin Machta, Christopher Lynn, Geoffery Fudenberg