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首页> 外文期刊>Molecular and Cellular Biology >Dynamic Loss of H2B Ubiquitylation without Corresponding Changes in H3K4 Trimethylation during Myogenic Differentiation
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Dynamic Loss of H2B Ubiquitylation without Corresponding Changes in H3K4 Trimethylation during Myogenic Differentiation

机译：H2B泛素化的动态损失，而在成肌分化过程中没有相应的H3K4三甲基化变化

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Ubiquitylation of H2B on lysine 120 (H2Bub) is associated with active transcriptional elongation. H2Bub has been implicated in histone cross talk and is generally regarded to be a prerequisite for trimethylation of histone 3 lysine 4 (H3K4me3) and H3K79 in both yeast and mammalian cells. We performed a genome-wide analysis of epigenetic marks during muscle differentiation, and strikingly, we observed a near-complete loss of H2Bub in the differentiated state. We examined the basis for global loss of this mark and found that the H2B ubiquitin E3 ligase, RNF20, was depleted from chromatin in differentiated myotubes, indicating that recruitment of this protein to genes substantially decreases upon differentiation. Remarkably, during the course of myogenic differentiation, we observed retention and acquisition of H3K4 trimethylation on a large number of genes in the absence of detectable H2Bub. The Set1 H3K4 trimethylase complex was efficiently recruited to a subset of genes in myotubes in the absence of detectable H2Bub, accounting in part for H3K4 trimethylation in myotubes. Our studies suggest that H3K4me3 deposition in the absence of detectable H2Bub in myotubes is mediated via Set1 and, perhaps, MLL complexes, whose recruitment does not require H2Bub. Thus, muscle cells represent a novel setting in which to explore mechanisms that regulate histone cross talk.
机译：H2B在赖氨酸120（H2Bub）上的泛素化与活跃的转录延伸有关。 H2Bub与组蛋白串扰有关，通常被认为是酵母和哺乳动物细胞中组蛋白3赖氨酸4（H3K4me3）和H3K79三甲基化的先决条件。我们在肌肉分化过程中对表观遗传标记进行了全基因组分析，而且引人注目的是，我们观察到分化状态下H2Bub几乎完全丧失。我们检查了该标记在全球范围内丢失的基础，发现H2B泛素E3连接酶RNF20在分化的肌管中已从染色质中耗尽，表明该蛋白质在基因上的募集在分化后会大大减少。值得注意的是，在成肌分化过程中，我们观察到在没有可检测的H2Bub的情况下，大量基因上H3K4三甲基化的保留和获得。在没有可检测的H2Bub的情况下，Set1 H3K4三甲基化酶复合物被有效地募集到肌管中的一个基因子集，部分解释了肌管中的H3K4三甲基化。我们的研究表明，在肌管中不存在可检测的H2Bub的情况下，H3K4me3的沉积是通过Set1以及可能与MLL复合物（其募集不需要H2Bub）介导的。因此，肌肉细胞代表了一种新颖的环境，可在其中探索调节组蛋白串扰的机制。

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