The UBP5 histone H2A deubiquitinase counteracts PRCs-mediated repression to regulate Arabidopsis development

Polycomb Repressive Complexes (PRCs) control gene expression through the incorporation of H2Aub and H3K27me3. In recent years, there is increasing evidence of the complexity of PRCs' interaction networks and the interplay of these interactors with PRCs in epigenome reshaping, which is fundamental to understand gene regulatory mechanisms. Here, we identified UBIQUITIN SPECIFIC PROTEASE 5 (UBP5) as a chromatin player able to counteract the deposition of the two PRCs' epigenetic hallmarks in Arabidopsis thaliana. We demonstrated that UBP5 is a plant developmental regulator based on functional analyses of ubp5-CRISPR Cas9 mutant plants. UBP5 promotes H2A monoubiquitination erasure, leading to transcriptional de-repression. Furthermore, preferential association of UBP5 at PRC2 recruiting motifs and local H3K27me3 gaining in ubp5 mutant plants suggest the existence of functional interplays between UBP5 and PRC2 in regulating epigenome dynamics. In summary, acting as an antagonist of the pivotal epigenetic repressive marks H2Aub and H3K27me3, UBP5 provides novel insights to disentangle the complex regulation of PRCs' activities. Overall design: Analysing the genome-wide occupancy of UBP5 using the ChIP-seq data from UBP5::UBP5-GFP;ubp5 lines.

多梳抑制复合体（Polycomb Repressive Complexes, PRCs）通过介导H2A单泛素化（H2Aub）和H3K27三甲基化（H3K27me3）修饰的沉积，调控基因表达。近年来，越来越多的研究证据表明，PRCs的互作网络具有高度复杂性，且这些互作因子与PRCs在表观基因组重塑过程中存在协同互作，这对于解析基因调控机制至关重要。本研究鉴定出泛素特异性蛋白酶5（UBIQUITIN SPECIFIC PROTEASE 5, UBP5）作为一类染色质调控因子，能够在拟南芥（Arabidopsis thaliana）中拮抗PRCs介导的两种表观遗传标志性修饰的沉积。通过对ubp5-CRISPR Cas9突变体植株的功能分析，我们证实UBP5是一类植物发育调控因子。UBP5可促进H2A单泛素化修饰的去除，进而解除基因转录抑制。此外，UBP5在PRC2招募基序处的优先结合，以及ubp5突变体中局部区域H3K27me3修饰水平的升高，表明UBP5与PRC2之间存在功能互作，共同调控表观基因组动态变化。综上，作为关键表观遗传抑制标记H2Aub和H3K27me3的拮抗因子，UBP5为解析PRCs活性的复杂调控网络提供了全新视角。实验整体设计：利用UBP5::UBP5-GFP;ubp5株系的染色质免疫共沉淀测序（ChIP-seq）数据，分析UBP5在全基因组范围内的结合分布。