多梳蛋白是一种基本的抑制系统，通过协调控制细胞身份的细胞类型特异性转录程序来发挥至关重要的发育作用。 Polycomb 活性的直接改变确实与人类病理有关，包括发育障碍和癌症。一般性 Polycomb 抑制由三种不同的活性协调，调节两种组蛋白翻译后修饰的沉积：组蛋白 H3 赖氨酸 27 (H3K27me3) 和组蛋白 H2A 赖氨酸 119 (H2AK119ub1) 的三甲基化。这些活性存在于大型且异质的多蛋白整体中，该整体由共同的酶核心组成，并受到异质非催化模块的调节，而异质非催化模块由大量具有不同生化特性的辅助蛋白组成。在这里，我们分析了当前的分子知识，重点关注核心酶活性及其由不同辅助模块介导的调节之间的功能相互作用。这提供了对控制 Polycomb 抑制的建立和维持的分子细节的全面分析，检查其潜在的协调并突出显示缺失的信息和 Polycomb 介导的转录控制的新特征。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Polycomb proteins are a fundamental repressive system that plays crucial developmental roles by orchestrating cell-type-specific transcription programs that govern cell identity. Direct alterations of Polycomb activity are indeed implicated in human pathologies, including developmental disorders and cancer. General Polycomb repression is coordinated by three distinct activities that regulate the deposition of two histone post-translational modifications: tri-methylation of histone H3 lysine 27 (H3K27me3) and histone H2A at lysine 119 (H2AK119ub1). These activities exist in large and heterogeneous multiprotein ensembles consisting of common enzymatic cores regulated by heterogeneous non-catalytic modules composed of a large number of accessory proteins with diverse biochemical properties. Here, we have analyzed the current molecular knowledge, focusing on the functional interaction between the core enzymatic activities and their regulation mediated by distinct accessory modules. This provides a comprehensive analysis of the molecular details that control the establishment and maintenance of Polycomb repression, examining their underlying coordination and highlighting missing information and emerging new features of Polycomb-mediated transcriptional control.Copyright © 2024 Elsevier Inc. All rights reserved.