The majority of our genome is composed of repeated DNA sequences that assemble into heterochromatin, a highly compacted structure that constrains their mutational potential. How heterochromatin forms during development and how its structure is maintained are not fully understood. Here, we show that mouse heterochromatin phase-separates after fertilization, during the earliest stages of mammalian embryogenesis. Using high-resolution quantitative imaging and molecular biology approaches, we show that pericentromeric heterochromatin displays properties consistent with a liquid-like state at the two-cell stage, which change at the four-cell stage, when chromocenters mature and heterochromatin becomes silent. Disrupting the condensates results in altered transcript levels of pericentromeric heterochromatin, suggesting a functional role for phase separation in heterochromatin function. Thus, our work shows that mouse heterochromatin forms membrane-less compartments with biophysical properties that change during development and provides new insights into the self-organization of chromatin domains during mammalian embryogenesis.

中文翻译：

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生物物理特性的变化伴随着小鼠胚胎中异染色质的形成

我们基因组的大部分由重复的 DNA 序列组成，这些序列组装成异染色质，这是一种高度紧凑的结构，限制了它们的突变潜力。异染色质在发育过程中如何形成以及其结构如何维持尚不完全清楚。在这里，我们发现小鼠异染色质在受精后、哺乳动物胚胎发生的最早阶段发生相分离。使用高分辨率定量成像和分子生物学方法，我们表明，着丝粒周围异染色质在两细胞阶段表现出与液体状态一致的特性，而在四细胞阶段，当染色中心成熟且异染色质变得沉默时，这种特性发生变化。破坏冷凝物会导致着丝粒周围异染色质的转录水平发生改变，这表明相分离在异染色质功能中的功能作用。因此，我们的工作表明，小鼠异染色质形成无膜区室，其生物物理特性在发育过程中发生变化，并为哺乳动物胚胎发生过程中染色质结构域的自组织提供了新的见解。