Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events
Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events
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DOI：
10.1038/nsmb.2310
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发表时间：
2012-08-01
影响因子：
16.8
通讯作者：
Selenko, Philipp
中科院分区：
文献类型：
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作者：
Liokatis, Stamatios;Stuetzer, Alexandra;Selenko, Philipp
组蛋白H3的Ser10磷酸化调节染色体凝聚和转录活性。使用时间分辨，高分辨率NMR光谱，我们证明，组蛋白H3 Ser10磷酸化抑制检查点激酶1（Chk1）和蛋白激酶C（PKC）介导的修饰Thr11和Thr6，这些激酶的主要底物位点。在未修饰的H3上，这两种酶也靶向Ser10，从而在单个H3尾上建立自抑制反馈状态。然而，磷酸化的Ser10不影响Gcn5对Lys14的乙酰化，磷酸化的Thr11阻碍乙酰化。我们的观察揭示了H3磷酸化和乙酰化事件的机制层次结构，并提供了一个框架内的组蛋白H3的N末端的分子内修饰串扰。
Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)- and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails. Whereas phosphorylated Ser10 does not affect acetylation of Lys14 by Gcn5, phosphorylated Thr11 impedes acetylation. Our observations reveal mechanistic hierarchies of H3 phosphorylation and acetylation events and provide a framework for intramolecular modification cross-talk within the N terminus of histone H3.