Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells
Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells
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DOI：
10.4161/cc.11.1.18402
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发表时间：
2012-01-01
期刊：
影响因子：
4.3
通讯作者：
Dai, Xing
中科院分区：
文献类型：
--
作者：
Gu, Bingnan;Watanabe, Kazuhide;Dai, Xing
组蛋白基因的表达在细胞周期中受到严格控制。这种调节的表观遗传机制仍有待充分阐明。Pygopus 2（Pygo 2）是Wnt/β-连环蛋白信号传导的上下文依赖性共激活剂和参与组蛋白修饰的染色质效应子。在这项研究中，我们表明，Pygo 2是需要在培养的人乳腺上皮细胞中的组蛋白基因的多个类的最佳表达。使用染色质免疫沉淀试验，我们证明Pygo 2直接占据多个组蛋白基因的启动子，并增强组蛋白H3（H3 K56 Ac）中赖氨酸56的乙酰化，以前显示，以促进酵母组蛋白基因在这些启动子的转录。此外，我们报告了Pygo 2耗尽细胞中H3 K56 Ac的总体水平降低，其以细胞周期无关的方式发生。总之，我们的数据揭示了哺乳动物组蛋白基因表达的一种新的调节剂，其可能部分通过修饰H3 K56 Ac起作用。
Histone gene expression is tightly controlled during cell cycle. The epigenetic mechanisms underlying this regulation remain to be fully elucidated. Pygopus 2 (Pygo2) is a context-dependent co-activator of Wnt/beta-catenin signaling and a chromatin effector that participates in histone modification. In this study, we show that Pygo2 is required for the optimal expression of multiple classes of histone genes in cultured human mammary epithelial cells. Using chromatin immunoprecipitation assay, we demonstrate that Pygo2 directly occupies the promoters of multiple histone genes and enhances the acetylation of lysine 56 in histone H3 (H3K56Ac), previously shown to facilitate yeast histone gene transcription at these promoters. Moreover, we report reduced global levels of H3K56Ac in Pygo2-depleted cells that occur in a cell cycle-independent manner. Together, our data uncover a novel regulator of mammalian histone gene expression that may act in part via modifying H3K56Ac.