Phase separation of chromatin brush driven by enzymatic reaction dynamics of histone posttranslational modifications

Abstract

The nuclei of undifferentiated cells show uniform decompacted chromatin while during development nuclei decrease in size and foci of condensed chromatin appear, reminiscent of phase separation. This study is motivated by recent experiments that suggest that the unbinding of enzymes that chemically modify (acetylate) histone tails causes decompaction of condensed chromatin. Here we take into account the enzymatic reactions of histone modifications to predict the phase separation of chromatin in a model system, the chromatin brush, which mimics chromatin at the proximity of a nuclear membrane. The model contains activators and silencers, which change the state of the nucleosomes to (transcriptionally) active or inactive via the Michaelis-Menten kinetics. Our theory predicts that the chromatin brush will phase separate when the brush height is reduced below a threshold height. The phase separation is driven by an anti-correlation: Activators change the state of nucleosomes to the active state suppressing the binding of silencers to these nucleosomes and vice versa.