Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&2 system, but its functional role remains elusive. We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.

中文翻译：

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在拟南芥中，需要通过泛素特异性蛋白酶 12 和 13 去除 H2Aub1，以实现稳定的 Polycomb 介导的基因抑制


稳定的基因抑制对于正常生长和发育至关重要。 Polycomb 抑制复合物 1 和 2 (PRC1&2) 通过建立组蛋白 2A (H2Aub1) 的单泛素化以及随后组蛋白 3 (H3K27me3) 的赖氨酸 27 的三甲基化来参与此过程。先前的工作提出，泛素特异性蛋白酶 12 和 13（UBP12 和 UBP13）消除 H2Aub1 是抑制 PRC1&2 系统的一部分，但其功能作用仍然难以捉摸。我们发现 UBP12 和 UBP13 与 PRC1、PRC2 和 EMF1 一起作用来抑制参与刺激反应的基因。我们发现 PRC1 介导的 H2Aub1 与基因反应性相关，其抑制功能需要 PRC2 招募。我们进一步表明，PRC1 对 PRC2 招募的要求取决于基因的初始表达状态。最后，我们证明 UBP12/13 去除 H2Aub1 可防止 H3K27me3 丢失，这与我们的发现一致，即 H3K27me3 去甲基酶 REF6 与 H2Aub1 呈正相关。我们的数据使我们能够提出一个模型，其中 H2Aub1 的沉积允许基因通过 H3K27me3 沉积和去除在抑制和激活之间切换。要实现 PRC2 介导的稳定抑制，需要 UBP12/13 去除 H2Aub1。