Polycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus; a conformation that is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organization and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb-repressive complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses, we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, while highlighting the complexity of this regulatory system.

中文翻译：

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规范 PRC1 在塑造 3D 核景观方面的核心作用。

Polycomb 组 (PcG) 蛋白通过化学和物理修饰染色质来沉默基因表达。PcG 目标基因座的一个子集被压缩并聚集在细胞核中；一种被认为有助于基因沉默的构象。然而，这些相互作用如何影响总核组织及其与转录的关系仍然知之甚少。在这里，我们研究了 Polycomb 抑制复合物 1 (PRC1) 在塑造小鼠胚胎干细胞 (mESC) 的 3D 基因组组织中的作用。通过结合成像和 Hi-C 分析，我们表明 PRC1 介导的远程相互作用独立于 CTCF，并且可以在兆碱基规模上桥接位点。PRC1 酶活性受损不会直接破坏这些相互作用。我们证明 PcG 目标在体内结合，并且目标基因座之一的发育诱导表达破坏了这种空间排列。最后，我们表明转录激活和 PRC1 介导的相互作用的丧失是可分离的事件。这些发现提供了对 PRC1 功能的重要见解，同时突出了该监管系统的复杂性。