Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination
Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination
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DOI：
10.1126/science.1149042
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发表时间：
2007-10-19
期刊：
影响因子：
56.9
通讯作者：
Shiekhattar, Ramin
中科院分区：
文献类型：
--
作者：
Lee, Min Gyu;Villa, Raffaella;Shiekhattar, Ramin
组蛋白H3赖氨酸27 （H3K27）的甲基化是一种与基因组沉默高度相关的翻译后修饰。在这里，我们发现人类UTX是一种二甲基和三甲基H3K27去甲基酶，它是Jumonji C蛋白家族的成员。UTX占据HOX基因簇的启动子，并通过调节多梳抑制复合体1的募集和组蛋白H2A的单泛素化来调节其转录输出。此外，UTX与混合谱系白血病（MLL） 2/3复合物相关，在维甲酸信号事件中，UTX复合物募集到HOX基因导致H3K27去甲基化和伴随的H3K4甲基化。我们的研究结果表明了一个协调一致的转录激活机制，其中MLL2/3的H3K4甲基化周期与通过UTX的H3K27去甲基化相关联。
Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. Moreover, UTX associates with mixed-lineage leukemia (MLL) 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.