英国牛津大学Robert J. Klose等研究人员合作发现，Polycomb系统通过限制预启动复合物的形成来维持启动子处于深度关闭状态以抑制转录。相关论文于2024年9月11日在线发表在《自然—细胞生物学》杂志上。

通过快速的基于降解标签的消耗方法，结合活细胞转录成像和单颗粒追踪技术，研究人员揭示了Polycomb系统如何在单个细胞中控制转录。研究人员发现，Polycomb系统并非持续阻断转录，而是维持启动子处于一种持久的深度关闭（OFF）状态，从而限制启动子进入转录状态的频率。

该研究表明，Polycomb通过对抗能够促进早期转录预启动复合物形成的因子的结合，来维持这一深度关闭状态，并且这一机制对基因抑制至关重要。这些重要发现为Polycomb系统如何控制转录提供了合理解释，并提出了一种可能在不同细胞环境中普遍适用的机制，能够限制转录。

据悉，Polycomb系统在哺乳动物发育过程中，对基因表达的调控起着至关重要的作用。然而，它如何控制转录以实现基因抑制仍然不明。

附：英文原文

Title: The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcripion

Author: Szczurek, Aleksander T., Dimitrova, Emilia, Kelley, Jessica R., Blackledge, Neil P., Klose, Robert J.

Issue&Volume: 2024-09-11

Abstract: The Polycomb system has fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here, using rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking, we show how the Polycomb system controls transcription in single cells. We discover that the Polycomb system is not a constitutive block to transcription but instead sustains a long-lived deep promoter OFF state, which limits the frequency with which the promoter can enter into a transcribing state. We demonstrate that Polycomb sustains this deep promoter OFF state by counteracting the binding of factors that enable early transcription pre-initiation complex formation and show that this is necessary for gene repression. Together, these important discoveries provide a rationale for how the Polycomb system controls transcription and suggests a universal mechanism that could enable the Polycomb system to constrain transcription across diverse cellular contexts.

DOI: 10.1038/s41556-024-01493-w

Source: https://www.nature.com/articles/s41556-024-01493-w