Fundación Ciencia para la Vida, Santiago 7780272, Chile.
J Biol Chem. 2011 May 20;286(20):17714-21. doi: 10.1074/jbc.M111.223453. Epub 2011 Mar 29.
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.
在核小体中组蛋白功能的研究已经取得了很大进展；然而，组蛋白在合成之后，其标记和亚细胞运输是如何被调控的，这仍然是一个待探索的问题。为了深入研究这些问题，我们专注于可溶组蛋白，并对内源性和标记的 H3 组蛋白进行平行分析。我们区分了六个复合物，可以解释从组蛋白 H3 和 H4 合成开始到成熟过程中发生的事件。在每个复合物中，涉及到不同的伴侣，我们发现了特定的翻译后修饰。有趣的是，我们揭示了组蛋白 H3 和 H4 是短暂的聚（ADP-核糖）化。这些标记在组蛋白代谢中的作用非常重要，因为我们发现组蛋白 H4 赖氨酸 5 和 12 的乙酰化可以刺激其核转位。此外，我们表明，根据特定的组蛋白 H3 修饰，不同转位复合物的存在平衡会发生变化。因此，我们的研究结果为控制细胞质/核穿梭和早期修饰模式的建立提供了这些标记的调控手段。
