Theoretical analysis of confinement mechanisms for epigenetic modifications of nucleosomes

Abstract

Nucleosomes and their modifications often facilitate gene regulation in eukaryotes. Certain genomic regions may obtain alternate epigenetic states through enzymatic reactions forming positive feedback between nucleosome states. How a system of nucleosome states maintains confinement is an open question. Here we explore a family of stochastic dynamic models with combinations of readwrite enzymes. We find that a larger number of intermediate nucleosome states increases both the robustness of linear spreading in models with only local recruitment processes and the degree of bi-stability under conditions with at least one non-local recruitment. Further, supplementing the positive feedback with one negative feedback acting over long distances along the genome enables effective confinement of epigenetic, bistable regions. Our study emphasizes the importance of determining whether each particular read-write enzyme acts only locally or between distant nucleosomes.