Condemi Livia, Mocavini Ivano, Aranda Sergi, Di Croce Luciano
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain.
Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Cell Death Differ. 2025 Jan;32(1):90-99. doi: 10.1038/s41418-024-01340-3. Epub 2024 Jul 12.
Epigenetic factors are crucial for ensuring proper chromatin dynamics during the initial stages of embryo development. Among these factors, the Polycomb group (PcG) of proteins plays a key role in establishing correct transcriptional programmes during mouse embryogenesis. PcG proteins are classified into two complexes: Polycomb repressive complex 1 (PRC1) and PRC2. Both complexes decorate histone proteins with distinct post-translational modifications (PTMs) that are predictive of a silent transcriptional chromatin state. In recent years, a critical adaptation of the classical techniques to analyse chromatin profiles and to study biochemical interactions at low-input resolution has allowed us to deeply explore PcG molecular mechanisms in the very early stages of mouse embryo development- from fertilisation to gastrulation, and from zygotic genome activation (ZGA) to specific lineages differentiation. These advancements provide a foundation for a deeper understanding of the fundamental role Polycomb complexes play in early development and have elucidated the mechanistic dynamics of PRC1 and PRC2. In this review, we discuss the functions and molecular mechanisms of both PRC1 and PRC2 during early mouse embryo development, integrating new studies with existing knowledge. Furthermore, we highlight the molecular functionality of Polycomb complexes from ZGA through gastrulation, with a particular focus on non-canonical imprinted and bivalent genes, and Hox cluster regulation.
表观遗传因素对于确保胚胎发育初始阶段染色质的正常动态变化至关重要。在这些因素中，多梳蛋白家族（PcG）在小鼠胚胎发生过程中建立正确的转录程序方面发挥着关键作用。PcG蛋白分为两个复合物：多梳抑制复合物1（PRC1）和PRC2。这两个复合物都通过独特的翻译后修饰（PTM）修饰组蛋白，这些修饰预示着沉默的转录染色质状态。近年来，经典技术的关键改进使得我们能够在低输入分辨率下分析染色质图谱并研究生化相互作用，从而深入探索小鼠胚胎发育极早期阶段——从受精到原肠胚形成，以及从合子基因组激活（ZGA）到特定谱系分化过程中的PcG分子机制。这些进展为更深入理解多梳复合物在早期发育中所起的基本作用奠定了基础，并阐明了PRC1和PRC2的机制动态。在本综述中，我们结合新研究与现有知识，讨论了PRC1和PRC2在小鼠胚胎早期发育过程中的功能和分子机制。此外，我们重点介绍了从ZGA到原肠胚形成过程中多梳复合物的分子功能，特别关注非经典印记基因和双价基因以及Hox基因簇调控。
