|DATE||July 30 (Thu), 2020|
|INSTITUTE||University of Texas, Austin|
|TITLE||Genome structure–function relationship revealed by an active Chromosome Copolymer Model|
A mammalian genome functions with specificity while exhibiting heterogeneous spatial organization. It is unclear how the structural and functional aspects of such complex genomes are related with each other. In this presentation, we highlight the interactive relationship between genome structure and function using coarse-grained polymer simulations under non-equilibrium conditions. We model a human interphase chromosome as an active Chromosome Copolymer Model (CCM) polymer where active force is applied to genetically open (euchromatin) loci to mimic transcription. We demonstrate that although the organizational features at large length scale such as compartments and TADs are preserved, active force can preferentially enhance the chromatin packing at small length scale (at the sub-TAD level), which stabilizes the interactions between cis-regulatory elements, and hence the transcription process of individual genes. We illustrate that this effect of transcriptional activity varies greatly depending on the chromosome conformation within a given cell as well as the loop formation at each CTCF binding site. Our study elucidates new quantitative insights into how genome structure and function influence each other for gene regulation.