The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanistically relevant features of pericentric heterochromatin compaction in mouse fibroblasts. We find that (1) HP1 has only a weak capacity to form liquid droplets in living cells; (2) the size, global accessibility, and compaction of heterochromatin foci are independent of HP1; (3) heterochromatin foci lack a separated liquid HP1 pool; and (4) heterochromatin compaction can toggle between two "digital" states depending on the presence of a strong transcriptional activator. These findings indicate that heterochromatin foci resemble collapsed polymer globules that are percolated with the same nucleoplasmic liquid as the surrounding euchromatin, which has implications for our understanding of chromatin compartmentalization and its functional consequences.

中文翻译：

---

小鼠异染色质采用数字压实状态，而没有表现出HP1驱动的液相分离的特征。

沉默和浓缩的异染色质病灶的形成涉及异染色质蛋白1（HP1）的富集。HP1可以桥接染色质片段并形成液滴，但是在细胞核中异染色质区室化基础的生物物理原理是难以捉摸的。在这里，我们评估在小鼠成纤维细胞中周围异染色质压实的机械相关特征。我们发现（1）HP1在活细胞中形成液滴的能力很弱；（2）异染色质病灶的大小，整体可及性和压实度独立于HP1；（3）异染色质病灶缺乏分离的液体HP1库；（4）异染色质紧实可以根据强转录激活因子的存在在两个“数字”状态之间切换。