State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON N5V 4T3, Canada.
Mol Cell. 2024 Sep 19;84(18):3438-3454.e8. doi: 10.1016/j.molcel.2024.08.018. Epub 2024 Sep 3.
Spreading of H3K27me3 is crucial for the maintenance of mitotically inheritable Polycomb-mediated chromatin silencing in animals and plants. However, how Polycomb repressive complex 2 (PRC2) accesses unmodified nucleosomes in spreading regions for spreading H3K27me3 remains unclear. Here, we show in Arabidopsis thaliana that the chromatin remodeler PICKLE (PKL) plays a specialized role in H3K27me3 spreading to safeguard cell identity during differentiation. PKL specifically localizes to H3K27me3 spreading regions but not to nucleation sites and physically associates with PRC2. Loss of PKL disrupts the occupancy of the PRC2 catalytic subunit CLF in spreading regions and leads to aberrant dedifferentiation. Nucleosome density increase endowed by the ATPase function of PKL ensures that unmodified nucleosomes are accessible to PRC2 catalytic activity for H3K27me3 spreading. Our findings demonstrate that PKL-dependent nucleosome compaction is critical for PRC2-mediated H3K27me3 read-and-write function in H3K27me3 spreading, thus revealing a mechanism by which repressive chromatin domains are established and propagated.
H3K27me3 的扩散对于动植物中维持有丝分裂可遗传的多梳抑制复合物（Polycomb）介导的染色质沉默至关重要。然而，多梳抑制复合物 2（PRC2）如何在扩散区域中访问未修饰的核小体以扩散 H3K27me3 仍然不清楚。在这里，我们在拟南芥中表明，染色质重塑因子 PICKLE（PKL）在 H3K27me3 扩散中发挥专门作用，以在分化过程中保护细胞身份。PKL 特异性定位于 H3K27me3 扩散区域，但不在核小体形成位点，并且与 PRC2 物理相关。PKL 的缺失破坏了 PRC2 催化亚基 CLF 在扩散区域中的占据，并导致异常的去分化。PKL 的 ATP 酶功能赋予的核小体密度增加确保了未修饰的核小体可被 PRC2 催化活性用于 H3K27me3 扩散。我们的发现表明，PKL 依赖性核小体紧缩对于 PRC2 介导的 H3K27me3 扩散中的 H3K27me3 读和写功能至关重要，从而揭示了抑制性染色质域建立和传播的机制。
