Histone trimethylation on the tail residue H3K9 of nucleosomes is a hallmark of constitutive heterochromatin. The mechanism how this mark is maintained over cell division cycles remains a topic of ongoing debate. The recent formulation of the polymer-assisted condensation (PAC) scenario, through which a stable droplet condensate can form as a reaction container for methylation reactions, has offered a novel approach to answer this longstanding question. In this letter we develop a kinetic proofreading argument for histone tail methylation which builds on the PAC model and yields support to the idea that liquid-liquid phase separation underlies the reconstitution of heterochromatin over cell division cycles.
Blossey et al. (2026) studied this question.