Epigenetic Silencing of Core Histone Genes by HERS in Drosophila
Epigenetic Silencing of Core Histone Genes by HERS in Drosophila
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DOI：
10.1016/j.molcel.2011.12.029
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发表时间：
2012-02-24
期刊：
影响因子：
16
通讯作者：
Kato, Shigeaki
中科院分区：
文献类型：
--
作者：
Ito, Saya;Fujiyama-Nakamura, Sally;Kato, Shigeaki
典型组蛋白的细胞周期依赖性表达使得新合成的DNA能够整合到复制细胞中的染色质中。然而，细胞周期依赖性的组蛋白基因调控开关的分子基础仍有待发现。在这里，我们报告了一个分子开关，HERS（（h）下bar istone基因特异性（e）下bar pigenetic（r）下bar抑制剂在后期（S）下bar阶段），在果蝇核小体核心组蛋白基因失活的鉴定和生化特性。HERS蛋白在S期结束时被细胞周期蛋白依赖性激酶（Cdk）磷酸化。磷酸化的HERS与组蛋白基因调控区结合并锚定HP 1和Su（var）3-9，以通过组蛋白H3赖氨酸9甲基化诱导染色质失活。这些发现说明了一个显着的分子开关连接表观遗传基因沉默细胞周期依赖性组蛋白的生产。
Cell cycle-dependent expression of canonical histone proteins enables newly synthesized DNA to be integrated into chromatin in replicating cells. However, the molecular basis of cell cycle-dependency in the switching of histone gene regulation remains to be uncovered. Here, we report the identification and biochemical characterization of a molecular switcher, HERS ((h) under bar istone gene-specific (e) under bar pigenetic (r) under bar epressor in late (S) under bar phase), for nucleosomal core histone gene inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin inactivation through histone H3 lysine 9 methylation. These findings illustrate a salient molecular switch linking epigenetic gene silencing to cell cycle-dependent histone production.