A Central Role for Canonical PRC1 in Shaping the 3D Nuclear Landscape
A Central Role for Canonical PRC1 in Shaping the 3D Nuclear Landscape
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Canonical PRC1 在塑造 3D 核景观方面的核心作用
DOI：
10.1101/2019.12.15.876771
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Boyle S
中科院分区：
文献类型：
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作者：
Boyle S
Polycomb group（PcG）蛋白通过化学和物理修饰染色质来沉默基因表达。PcG靶基因座的一个子集在细胞核中被压缩并聚集;这种构象被认为有助于基因沉默。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-repressive complex 1（PRC 1）在小鼠胚胎干细胞（mESC）中塑造3D基因组组织的作用。使用成像和Hi-C分析的组合，我们表明PRC 1介导的长程相互作用是独立的CTCF，并可以在兆兆规模的桥梁网站。PRC 1酶活性的损害不会直接破坏这些相互作用。我们证明，PcG目标聚结在体内，发育诱导的表达的目标基因座之一，破坏这种空间排列。最后，我们表明，转录激活和PRC 1介导的相互作用的损失是可分离的事件。这些发现为PRC 1的功能提供了重要的见解，同时突出了这个调控系统的复杂性。
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.