Abstract
In multicellular organisms, nucleosomes, the building blocks of chromatin, carry epigenetic information, defining distinct patterns of gene expression, that are inherited over many generations. The enhanced capacity for information storage arises by modification of nucleosomes triggered by specific enzymes. Nucleosomes in a modified state can transfer the mark to other nucleosomes that are in proximity by a positive feedback (modification begets modification) mechanism. We created a polymer model in which each bead represents a nucleosomes with a specific nucleation site (NS) that is permanently in the modified state. All other nucleosomes stochastically switch between an unmodified (U) and M state. If the rate of spreading, which is initiated at the NS, is much faster than the polymer relaxation rate, domains containing the modified nucleosomes form without bound. In the opposite limit, finite-sized modified domains emerge, with the chromatin remaining in an expanded state, by a positive feedback mechanism involving contacts between nucleosomes through a looping mechanism. Surprisingly, we predict that the bounded domains arise without the need for any boundary elements as long as the spreading is slow. It is also shown that maintenance of spatially and temporally stable domains require the presence of the NS whose removal eliminates the formation of finite-sized modified domains. Our computational framework elucidates potential scenarios, which could be used to explain epigenetic patterns in some species.
Competing Interest Statement
The authors have declared no competing interest.
