Fig. 1: Schematic description of model ingredients.

a Schematic of a portion of a nucleus showing the multiple mechanisms involved in chromatin organization such as chromatin-chromatin interactions, the chromatin-lamina interactions and epigenetic regulation. Additionally, extrusion of chromatin loops due to DNA supercoiling – which is increased by transcriptional activity – also plays a role in meso-scale genomic organization. While this may occur within either chromatin phases (red circle), we further explore the role of chromatin loop extrusion at the heterochromatin-euchromatin interface (black circle). b The model captures the chromatin-chromatin interaction energetics via a double well free energy description as shown in the contour plot. The two wells correspond to the heterochromatin (red circle) and euchromatin phases (blue circle). Any initial configuration (light blue circle) spontaneously decomposes into these wells at steady state. The dynamics of this transition are governed by diffusion and reaction kinetics comprising of epigenetic regulation and kinetics of supercoiling-driven chromatin extrusion (red box inset). c Loading of cohesin assisted by NIPBL/MAU2 initiates the formation of chromatin loops. Cohesin can also be dynamically unloaded via unloading factors viz. WAPL/PDS5. Active processes such as RNAPII mediated transcription further drive the extrusion of trapped DNA, supercoiling it into chromatin loops.