How to correctly simulate local chromosome organization with minimal computing effort: lessons from crumpled polymer physics.

Gene regulation is highly dependent on the multi-scale 3D organization of chromosomes. In higher eukaryotes, biochemical modifications of the chromatin -epigenomic marks, modulate DNA accessibility thus transcription. Recent experimental evidence suggested that 1D epigenomic information, 3D genome folding and the formation of nuclear spatial compartments are coupled, but the mechanisms driving this coupling remain elusive. In my work, I employ polymer physics simulations to address this question. Often, biologically, genes or regions of interest are much smaller compared to the full length of a chromosome. Since (1) simulating long polymers (a full chromosome) for a biologically-relevant-long time period (hours) requires a lot of computing effort and that (2) the physics of long, topologically-constraint, aka crumpled, polymers differs from standard polymer theory, we address the theoretical question of what is the minimal genomic region around a locus of interest that one should simulate to effectively capture the correct dynamical and structural properties of this locus. We show that this minimal size depends on the overall epigenomic context and of the entanglement properties of the long polymer. We then show how our model can be contextualized to specific biological systems.