The lncRNA Xist forms ∼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain ∼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.

lncRNA Xist形成约 50 个衍射限制焦点，以转录沉默一条 X 染色体。这些少量的 RNA 焦点和相互作用的蛋白质如何调节大量的 X 连锁基因尚不清楚。我们发现Xist病灶是局部受限的，包含~2 个 RNA 分子和核超分子复合物 (SMAC)，其中包含许多关键沉默蛋白 SPEN 的拷贝。 SMAC 蛋白的聚集和交换产生局部蛋白梯度，调节广泛的近端染色质区域。许多 SPEN 分子划分为 SMAC 是由其本质上无序的区域介导的，这对于转录抑制至关重要。通过 SMAC 的多梳沉积会诱导染色质压缩和基因周围 SMAC 密度的增加，从而在 X 染色体上传播沉默。我们的研究结果引入了一种功能性核区室化机制，通过这种机制，转录和结构调节因子的拥挤使得少数 RNA 分子能够沉默许多靶基因。