BACKGROUND While the role of Polycomb group protein-mediated "cell memory" is well established in developmental contexts, little is known about their role in adult tissues and in particular in post-mitotic cells. Emerging evidence assigns a pivotal role in cell plasticity and adaptation. PRC2-Ezh1α/β signaling pathway from cytoplasm to chromatin protects skeletal muscle cells from oxidative stress. However, detailed mechanisms controlling degradation of cytoplasmic Ezh1β and assembly of canonical PRC2-Ezh1α repressive complex remain to be clarified. RESULTS Here, we report NEDD4 ubiquitin E3 ligase, as key regulator of Ezh1β. In addition, we report that ubiquitination and degradation of Ezh1β is controlled by another layer of regulation, that is, one specific phosphorylation of serine 560 located at Ezh1β-specific C terminal. Finally, we demonstrate that also Ezh1α needs to be stabilized under stress condition and this stabilization process requires decreased association pattern between another E3 ubiquitin ligase HUWE1. CONCLUSIONS Together, these results shed light on key components that regulate PRC2-Ezh1α/β pathway to direct modulation of epigenome plasticity and transcriptional output in skeletal muscle cells.

中文翻译：

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泛素连接酶HUWE1和NEDD4共同控制骨骼肌细胞中信号依赖的PRC2-Ezh1α/β介导的适应性应激反应途径。

背景技术尽管在发展背景中已经很好地确立了多梳基团蛋白介导的“细胞记忆”的作用，但关于它们在成年组织中，特别是在有丝分裂后细胞中的作用知之甚少。新兴证据在细胞可塑性和适应性中起着举足轻重的作用。从细胞质到染色质的PRC2-Ezh1α/β信号通路可保护骨骼肌细胞免受氧化应激。但是，控制细胞质Ezh1β降解和规范的PRC2-Ezh1α阻抑复合物装配的详细机制仍有待阐明。结果在这里，我们报道NEDD4泛素E3连接酶是Ezh1β的关键调控因子。此外，我们报道了Ezh1β的泛素化和降解受另一层调控，即位于Ezh1β特定C端的丝氨酸560的一个特定磷酸化。最后，我们证明了在应激条件下也需要稳定Ezh1α，并且该稳定过程需要减少另一个E3泛素连接酶HUWE1之间的缔合模式。结论综上所述，这些结果揭示了调节PRC2-Ezh1α/β通路直接调控表观基因组可塑性和骨骼肌细胞转录输出的关键成分。