School of Life Science, Shanxi University, Taiyuan, Shanxi 030006, China.
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2021 Jun 4;49(10):5407-5425. doi: 10.1093/nar/gkaa1262.
Polycomb group (PcG) proteins are widely utilized for transcriptional repression in eukaryotes. Here, we characterize, in the protist Tetrahymena thermophila, the EZL1 (E(z)-like 1) complex, with components conserved in metazoan Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The EZL1 complex is required for histone H3 K27 and K9 methylation, heterochromatin formation, transposable element control, and programmed genome rearrangement. The EZL1 complex interacts with EMA1, a helicase required for RNA interference (RNAi). This interaction is implicated in co-transcriptional recruitment of the EZL1 complex. Binding of H3K27 and H3K9 methylation by PDD1-another PcG protein interacting with the EZL1 complex-reinforces its chromatin association. The EZL1 complex is an integral part of Polycomb bodies, which exhibit dynamic distribution in Tetrahymena development: Their dispersion is driven by chromatin association, while their coalescence by PDD1, likely via phase separation. Our results provide a molecular mechanism connecting RNAi and Polycomb repression, which coordinately regulate nuclear bodies and reorganize the genome.
多梳抑制复合物（PcG）蛋白在真核生物中广泛用于转录抑制。在这里，我们在原生动物嗜热四膜虫中描述了 EZL1（E(z)-样 1）复合物，该复合物的成分在后生动物多梳抑制复合物 1 和 2（PRC1 和 PRC2）中保守。EZL1 复合物对于组蛋白 H3 K27 和 K9 甲基化、异染色质形成、转座元件控制和程序性基因组重排是必需的。EZL1 复合物与 EMA1 相互作用，后者是 RNA 干扰（RNAi）所必需的解旋酶。这种相互作用暗示了 EZL1 复合物在转录过程中的共招募。另一个与 EZL1 复合物相互作用的 PcG 蛋白 PDD1 通过结合 H3K27 和 H3K9 甲基化来增强其染色质结合。EZL1 复合物是多梳体的一个组成部分，在嗜热四膜虫的发育过程中表现出动态分布：它们的分散是由染色质结合驱动的，而它们的凝聚是由 PDD1 驱动的，可能通过相分离实现。我们的研究结果提供了一个连接 RNAi 和 Polycomb 抑制的分子机制，它们协调调节核体并重组基因组。
