Sequential establishment of marks on soluble histones H3 and H4.
Sequential establishment of marks on soluble histones H3 and H4.
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DOI：
10.1074/jbc.m111.223453
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发表时间：
2011-05-20
期刊：
影响因子：
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通讯作者：
Loyola A
中科院分区：
文献类型：
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作者：
Alvarez F;Muñoz F;Schilcher P;Imhof A;Almouzni G;Loyola A
组蛋白在细胞核中的功能已经取得了很大的进展；然而，在它们的合成之后，它们的标记和亚细胞运输如何被调控仍有待探索。为了深入了解这些问题，我们将重点放在了可溶性组蛋白上，并平行分析了内源性和标记的H3组蛋白。我们区分了六个复合体，我们可以用它们的合成来解释组蛋白H3和H4上发生的成熟事件。在每个复合体中，都涉及一组不同的伴侣，我们发现了特定的翻译后修饰。有趣的是，我们发现组蛋白H3和H4是瞬时多聚(ADP-核糖化)的。这些标记在组蛋白代谢中的影响被证明是重要的，因为我们发现赖氨酸5和12在组蛋白H4上的乙酰化刺激了它的核转位。此外，我们还表明，依赖于特定的组蛋白H3修饰，不同易位复合体存在时的平衡会发生变化。因此，我们的结果使我们能够提出一种调控这些标记的方法来控制细胞质/核的穿梭，并建立早期修饰模式。
Much progress has been made concerning histone function in the nucleus; however, following their synthesis, how their marking and subcellular trafficking are regulated remains to be explored. To gain an insight into these issues, we focused on soluble histones and analyzed endogenous and tagged H3 histones in parallel. We distinguished six complexes that we could place to account for maturation events occurring on histones H3 and H4 from their synthesis onward. In each complex, a different set of chaperones is involved, and we found specific post-translational modifications. Interestingly, we revealed that histones H3 and H4 are transiently poly(ADP-ribosylated). The impact of these marks in histone metabolism proved to be important as we found that acetylation of lysines 5 and 12 on histone H4 stimulated its nuclear translocation. Furthermore, we showed that, depending on particular histone H3 modifications, the balance in the presence of the different translocation complexes changes. Therefore, our results enabled us to propose a regulatory means of these marks for controlling cytoplasmic/nuclear shuttling and the establishment of early modification patterns.