Departments of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033, USA.
Penn State Hershey Cancer Institute, Hershey, PA 17033, USA.
Int J Mol Sci. 2020 Nov 14;21(22):8594. doi: 10.3390/ijms21228594.
Polycomb group (PcG) proteins function as vital epigenetic regulators in various biological processes, including pluripotency, development, and carcinogenesis. PcG proteins form multicomponent complexes, and two major types of protein complexes have been identified in mammals to date, Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The PRC1 complexes are composed in a hierarchical manner in which the catalytic core, RING1A/B, exclusively interacts with one of six Polycomb group RING finger (PCGF) proteins. This association with specific PCGF proteins allows for PRC1 to be subdivided into six distinct groups, each with their own unique modes of action arising from the distinct set of associated proteins. Historically, PRC1 was considered to be a transcription repressor that deposited monoubiquitylation of histone H2A at lysine 119 (H2AK119ub1) and compacted local chromatin. More recently, there is increasing evidence that demonstrates the transcription activation role of PRC1. Moreover, studies on the higher-order chromatin structure have revealed a new function for PRC1 in mediating long-range interactions. This provides a different perspective regarding both the transcription activation and repression characteristics of PRC1. This review summarizes new advancements regarding the composition of mammalian PRC1 and accompanying explanations of how diverse PRC1-associated proteins participate in distinct transcription regulation mechanisms.
多梳抑制复合物（PcG）蛋白在各种生物学过程中发挥着重要的表观遗传调控作用，包括多能性、发育和致癌作用。PcG 蛋白形成多组分复合物，迄今为止，在哺乳动物中已鉴定出两种主要类型的蛋白复合物，多梳抑制复合物 1 和 2（PRC1 和 PRC2）。PRC1 复合物以分层的方式组成，其中催化核心 RING1A/B 仅与六个多梳组 RING 指（PCGF）蛋白之一相互作用。这种与特定 PCGF 蛋白的结合允许 PRC1 被细分为六个不同的组，每个组都有其独特的作用模式，源自独特的相关蛋白组。历史上，PRC1 被认为是一种转录抑制剂，它在赖氨酸 119 处沉积组蛋白 H2A 的单泛素化（H2AK119ub1）并使局部染色质紧凑。最近，越来越多的证据表明 PRC1 具有转录激活作用。此外，对高级染色质结构的研究揭示了 PRC1 在介导长距离相互作用中的新功能。这为 PRC1 的转录激活和抑制特性提供了不同的视角。本综述总结了关于哺乳动物 PRC1 的组成的新进展，并解释了不同的 PRC1 相关蛋白如何参与不同的转录调控机制。
