Enzymatic activity in chromatin organization

Spatial organization of chromatin is critical for genome regulation. In literature, various types of affinity mediators and enzymes have been attributed for spatial organization of chromatin from thermodynamics perspective. However, at the mechanistic level, enzymes act in their unique ways. Here, we construct a polymer physics model following the mechanistic scheme of Topoisomerase-II, an enzyme resolving topological constraints of chromatin, and investigate its role on interphase chromatin organization. Our computer simulations demonstrate Topoisomerase-II's calibre in phase separating chromatin into eu- and heterochromatic regions with a characteristic wall-like organization of the euchromatic regions. We argue that transient phantomness of the euchromatin due to enzymatic activity of Topoisomerase-II induces this phase separation. Motivated from a recent experimental report, we further extend our model to a bidisperse setting and show that the characteristic features of the enzymatic activity driven phase separation survives there. The existence of these characteristic features, even under the non-localized action of the enzyme, highlights the critical role of enzymatic activity in chromatin organization, and points out the importance of further experiments along this line.