Chromatin dynamics controls epigenetic domain formation

In multicellular organisms, nucleosomes carry epigenetic information that defines distinct patterns of gene expression, which are inherited over multiple generations. The enhanced capacity for information storage arises by nucleosome modifications, triggered by enzymes. Modified nucleosomes can transfer the mark to others that are in proximity by a positive feedback (modification begets modification) mechanism. We created a polymer model in which each bead, representing a nucleosome, stochastically switches between unmodified (U) and modified (M) states depending on the states of the neighbors. Spreading is initiated at a specific nucleation site (NS) that is permanently in the M state. Modifications spread among the non-nucleation loci probabilistically. If the spreading rate is higher than the chromatin relaxation rate, domains containing the modified nucleosomes form without bound. In the opposite biologically relevant limit, finite-sized domains form, driven by contacts between nucleosomes through a three-dimensional looping mechanism, with chromatin remaining in an expanded state, as is appropriate for fission yeast. Surprisingly, finite bounded domains arise without the need for any boundary elements as long as the spreading is slow. Maintenance of spatially and temporally stable domains require the presence of the NS whose removal eliminates finite-sized modified domains. By varying the solvent quality we show that finite heterochromatin domains form as long as initially chromatin is not fully condensed. The predictions compare well with experimental data for H3K9me3 spreading in Mouse Embryonic Stem cell.