The polycomb group protein EZH2 is required for mammalian circadian clock function
The polycomb group protein EZH2 is required for mammalian circadian clock function
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DOI：
10.1074/jbc.m603722200
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发表时间：
2006-07-28
影响因子：
4.8
通讯作者：
Reppert, Steven M.
中科院分区：
文献类型：
--
作者：
Etchegaray, Jean-Pierre;Yang, Xiaoming;Reppert, Steven M.
我们研究了多梳蛋白组蛋白甲基化在小鼠生物钟机制中的重要性。内源性EZH2是一种多梳蛋白组酶，可使组蛋白H3上的赖氨酸27甲基化，在肝细胞核提取物中，它在整个昼夜节律周期中都与CLOCK和BMAL1共免疫沉淀。染色质免疫沉淀显示，EZH2结合在Period 1和Period 2启动子上，并且H3K27发生二甲基化和三甲基化。过表达和RNA干扰研究支持了EZH2在隐花色素介导的生物钟转录抑制中的作用。在培养的NIH 3T3细胞中，血清诱导的昼夜节律因转染靶向EZH2的RNA干扰序列而被打乱。这些结果表明，EZH2对维持昼夜节律很重要，并将多梳蛋白的活性扩展到哺乳动物的核心生物钟机制。
We examined the importance of histone methylation by the polycomb group proteins in the mouse circadian clock mechanism. Endogenous EZH2, a polycomb group enzyme that methylates lysine 27 on histone H3, co-immunoprecipitates with CLOCK and BMAL1 throughout the circadian cycle in liver nuclear extracts. Chromatin immunoprecipitation revealed EZH2 binding and di- and trimethylation of H3K27 on both the Period 1 and Period 2 promoters. A role of EZH2 in cryptochrome-mediated transcriptional repression of the clockwork was supported by overexpression and RNA interference studies. Serum-induced circadian rhythms in NIH 3T3 cells in culture were disrupted by transfection of an RNA interfering sequence targeting EZH2. These results indicate that EZH2 is important for the maintenance of circadian rhythms and extend the activity of the polycomb group proteins to the core clockwork mechanism of mammals.