Ectopic histone H3S10 phosphorylation causes chromatin structure remodeling in Drosophila
Ectopic histone H3S10 phosphorylation causes chromatin structure remodeling in Drosophila
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DOI：
10.1242/dev.015362
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发表时间：
2008-02-15
期刊：
影响因子：
4.6
通讯作者：
Johansen, Kristen M.
中科院分区：
文献类型：
--
作者：
Deng, Huai;Bao, Xiaomin;Johansen, Kristen M.
组蛋白经历许多翻译后修饰，这些修饰与高级染色质结构和基因表达的状态相关。然而，尚不清楚这些表观遗传标记的变化是否是染色质结构变化的调节因子，或者它们是否主要起增强或维持作用。在果蝇中，常染色质区域中的组蛋白H3 S10被JIL-1串联激酶磷酸化，这与抵消异染色质化和基因沉默有关。在这里，我们表明，使用LacI-系链系统，JIL-1介导的异位组蛋白H3 S10磷酸化足以诱导高阶染色质结构的变化，从凝聚异染色质样状态到更开放的常染色质状态。当表达没有组蛋白H3 S10磷酸化活性的“激酶死亡”LacI-JIL-1构建体时，这种作用不存在。相反，“激酶死亡”构建体具有显性负效应，导致染色质结构的破坏，这与组蛋白H3 S10磷酸化水平的整体抑制有关。这些研究结果提供了直接的证据表明，H3 S10磷酸化在间期的表观遗传组蛋白尾部修饰可以作为果蝇体内高阶染色质结构的致病调节剂。
Histones are subject to numerous post-translational modifications that correlate with the state of higher-order chromatin structure and gene expression. However, it is not clear whether changes in these epigenetic marks are causative regulatory factors in chromatin structure changes or whether they play a mainly reinforcing or maintenance role. In Drosophila phosphorylation of histone H3S10 in euchromatic chromatin regions by the JIL-1 tandem kinase has been implicated in counteracting heterochromatization and gene silencing. Here we show, using a LacI-tethering system, that JIL-1 mediated ectopic histone H3S10 phosphorylation is sufficient to induce a change in higher-order chromatin structure from a condensed heterochromatin-like state to a more open euchromatic state. This effect was absent when a 'kinase dead' LacI-JIL-1 construct without histone H3S10 phosphorylation activity was expressed. Instead, the 'kinase dead' construct had a dominant-negative effect, leading to a disruption of chromatin structure that was associated with a global repression of histone H3S10 phosphorylation levels. These findings provide direct evidence that the epigenetic histone tail modification of H3S10 phosphorylation at interphase can function as a causative regulator of higher-order chromatin structure in Drosophila in vivo.