Polycomb group (PcG) proteins silence master regulatory genes required to properly confer cell identity during the development of both Drosophila and mammals. They may act through chromatin compaction and higher-order folding of chromatin inside the cell nucleus. During the last decade, analysis on interphase chromosome architecture discovered self-interacting regions named topologically associated domains (TADs). TADs result from the 3D chromatin folding of a succession of transcribed and repressed epigenomic domains and from loop extrusion mediated by cohesin/CTCF in mammals. Polycomb silenced chromatin constitutes one type of repressed epigenomic domains which form compacted nano-compartments inside cell nuclei. Recruitment of canonical PcG proteins on chromatin relies on initial binding to discrete elements and further spreading into large chromatin domains covered with H3K27me3. Some of these discrete elements have a bivalent nature both in mammals and Drosophila and are dynamically regulated during development. Loops can occur between them, suggesting that their interaction plays both functional and structural roles. Formation of large chromatin domains covered by H3K27me3 seems crucial for PcG silencing and PcG proteins might exert their function through compaction of these domains in both mammals and flies, rather than by directly controlling the nucleosomal accessibility of discrete regulatory elements. In addition, PcG chromatin domains interact over long genomic distances, shaping a higher-order chromatin network. Therefore, PcG silencing might rely on multiscale chromatin folding to maintain cell identity during differentiation.

多梳族 (PcG) 蛋白可沉默果蝇和哺乳动物发育过程中正确赋予细胞身份所需的主调控基因。它们可能通过染色质压缩和细胞核内染色质的高阶折叠起作用。在过去的十年中，对间期染色体结构的分析发现了称为拓扑相关域（TAD）的自相互作用区域。 TAD 是由一系列转录和抑制的表观基因组结构域的 3D 染色质折叠以及哺乳动物中粘连蛋白/CTCF 介导的环挤出产生的。多梳沉默染色质构成一种受抑制的表观基因组结构域，在细胞核内形成致密的纳米隔室。染色质上经典 PcG 蛋白的募集依赖于与离散元件的初始结合，并进一步扩散到覆盖有 H3K27me3 的大染色质结构域中。其中一些离散元件在哺乳动物和果蝇中都具有二价性质，并且在发育过程中受到动态调节。它们之间可能出现循环，表明它们的相互作用同时发挥功能和结构作用。 H3K27me3 覆盖的大染色质结构域的形成似乎对于 PcG 沉默至关重要，并且 PcG 蛋白可能通过在哺乳动物和果蝇中压缩这些结构域来发挥其功能，而不是通过直接控制离散调节元件的核小体可及性。此外，PcG 染色质结构域在长基因组距离上相互作用，形成更高阶的染色质网络。因此，PcG 沉默可能依赖于多尺度染色质折叠来维持分化过程中的细胞身份。