This letter develops a kinetic proofreading argument for methylation in heterochromatin, suggesting implications for chromatin stability during cell division.
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.
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Blossey et al. (2026) studied this question.
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