The Polycomb repressive system plays a fundamental role in controlling gene expression during mammalian development. To achieve this, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) bind target genes and use histone modification-dependent feedback mechanisms to form Polycomb chromatin domains and repress transcription. The interrelatedness of PRC1 and PRC2 activity at these sites has made it difficult to discover the specific components of Polycomb chromatin domains that drive gene repression and to understand mechanistically how this is achieved. Here, by exploiting rapid degron-based approaches and time-resolved genomics we kinetically dissect Polycomb-mediated repression and discover that PRC1 functions independently of PRC2 to counteract RNA polymerase II binding and transcription initiation. Using single-cell gene expression analysis, we reveal that PRC1 acts uniformly within the cell population, and that repression is achieved by controlling transcriptional burst frequency. These important new discoveries provide a mechanistic and conceptual framework for Polycomb-dependent transcriptional control.

中文翻译：

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PRC1通过控制转录起始和猝发频率来驱动Polycomb介导的基因阻遏

在哺乳动物发育过程中，Polycomb抑制系统在控制基因表达中起着基本作用。为此，Polycomb阻抑复合物1和2（PRC1和PRC2）结合靶基因，并使用依赖组蛋白修饰的反馈机制形成Polycomb染色质域并抑制转录。在这些位点的PRC1和PRC2活性相互关联，使得很难发现驱动基因阻抑的聚梳染色质域的特定组成部分，并且很难从机械上理解这一点。在这里，通过利用快速的基于德龙的方法和时间分辨的基因组学，我们在动力学上剖析了Polycomb介导的阻遏作用，并发现PRC1独立于PRC2发挥功能来抵消RNA聚合酶II的结合和转录起始。使用单细胞基因表达分析，我们揭示PRC1在细胞群内均匀作用，并通过控制转录猝发频率来实现抑制。这些重要的新发现为Polycomb依赖的转录控制提供了一个机制和概念框架。