How enzymatic activity is involved in chromatin organization

Area of Science:

• Genomics
• Polymer Physics
• Molecular Biology

Background:

• Chromatin's spatial organization is crucial for genome regulation.
• Enzymes and affinity mediators influence chromatin organization thermodynamically.
• Enzymes mechanistically perturb chromatin structure.

Purpose of the Study:

• To model the mechanistic effects of Topoisomerase-II on interphase chromatin organization.
• To investigate how Topoisomerase-II activity induces chromatin phase separation.

Main Methods:

• Constructed a polymer physics model based on Topoisomerase-II's mechanism.
• Performed computer simulations of chromatin organization.
• Extended the model to a bidisperse setting.

Main Results:

• Topoisomerase-II activity promotes phase separation of chromatin into eu- and heterochromatic regions.
• Euchromatic regions exhibit a characteristic wall-like organization.
• Enzymatic activity-induced phase separation features persist in a bidisperse model.

Conclusions:

• Topoisomerase-II's ability to resolve topological constraints drives chromatin phase separation.
• The physical principle of reduced self-avoiding interactions underlies this phase separation.
• Enzymatic activity plays a critical and robust role in chromatin organization.