Correlative evidence has suggested that the methyl-CpG-binding protein MeCP2 contributes to the formation of heterochromatin condensates via liquid-liquid phase separation. This interpretation has been reinforced by the observation that heterochromatin, DNA methylation and MeCP2 co-localise within prominent foci in mouse cells. The findings presented here revise this view. MeCP2 localisation is independent of heterochromatin as MeCP2 foci persist even when heterochromatin organisation is disrupted. Additionally, MeCP2 foci fail to show hallmarks of phase separation in live cells. Importantly, we find that mouse cellular models are highly atypical as MeCP2 distribution is diffuse in most mammalian species, including humans. Notably, MeCP2 foci are absent in Mus spretus which is a mouse subspecies lacking methylated satellite DNA repeats. We conclude that MeCP2 has no intrinsic tendency to form condensates and its localisation is independent of heterochromatin. Instead, the distribution of MeCP2 in the nucleus is primarily determined by global DNA methylation patterns.

相关证据表明，甲基CpG结合蛋白MeCP2有助于通过液-液相分离形成异染色质凝聚物。异染色质、DNA 甲基化和 MeCP2 在小鼠细胞的显着灶内共定位的观察结果强化了这一解释。这里提出的研究结果修正了这一观点。 MeCP2 定位独立于异染色质，因为即使异染色质组织被破坏，MeCP2 焦点仍然存在。此外，MeCP2 焦点未能显示活细胞中相分离的特征。重要的是，我们发现小鼠细胞模型高度非典型，因为 MeCP2 分布在大多数哺乳动物物种（包括人类）中是分散的。值得注意的是，MeCP2 焦点在Mus spretus中不存在，这是一种缺乏甲基化卫星 DNA 重复序列的小鼠亚种。我们得出结论，MeCP2 没有形成凝聚物的内在倾向，并且其定位与异染色质无关。相反，MeCP2 在细胞核中的分布主要由整体 DNA 甲基化模式决定。