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首页> 外文期刊>Molecular and Cellular Biology >Ezh2 Requires PHF1 To Efficiently Catalyze H3 Lysine 27 Trimethylation In Vivo
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Ezh2 Requires PHF1 To Efficiently Catalyze H3 Lysine 27 Trimethylation In Vivo

机译：Ezh2需要PHF1有效体内催化H3赖氨酸27三甲基化

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The mammalian Polycomblike protein PHF1 was previously shown to interact with the Polycomb group (PcG) protein Ezh2, a histone methyltransferase whose activity is pivotal in sustaining gene repression during development and in adulthood. As Ezh2 is active only when part of the Polycomb Repressive Complexes (PRC2-PRC4), we examined the functional role of its interaction with PHF1. Chromatin immunoprecipitation experiments revealed that PHF1 resides along with Ezh2 at Ezh2-regulated genes such as the HoxA loci and the non-Hox MYT1 and WNT1 genes. Knockdown of PHF1 or of Ezh2 led to up-regulated HoxA gene expression. Interestingly, depletion of PHF1 did correlate with reduced occupancy of Bmi-1, a PRC1 component. As expected, knockdown of Ezh2 led to reduced levels of its catalytic products H3K27me2/H3K27me3. However, reduced levels of PHF1 also led to decreased global levels of H3K27me3. Notably, the levels of H3K27me3 decreased while those of H3K27me2 increased at the up-regulated HoxA loci tested. Consistent with this, the addition of PHF1 specifically stimulated the ability of Ezh2 to catalyze H3K27me3 but not H3K27me1/H3K27me2 in vitro. We conclude that PHF1 modulates the activity of Ezh2 in favor of the repressive H3K27me3 mark. Thus, we propose that PHF1 is a determinant in PcG-mediated gene repression.
机译：先前已证明哺乳动物的Polycomblike蛋白PHF1与Polycomb group（PcG）蛋白Ezh2相互作用，Ezh2是一种组蛋白甲基转移酶，其活性在维持发育过程和成年期的基因抑制中至关重要。由于Ezh2仅在部分Polycomb Repressive Complexs（PRC2-PRC4）时才具有活性，因此我们检查了其与PHF1相互作用的功能作用。染色质免疫沉淀实验表明，PHF1与Ezh2一起存在于Ezh2调控的基因上，例如HoxA基因座，非Hox MYT1和WNT1基因。击倒PHF1或Ezh2导致HoxA基因表达上调。有趣的是，PHF1的消耗确实与Bmi-1（PRC1的组成部分）的占用减少有关。不出所料，Ezh2的敲低导致其催化产物H3K27me2 / H3K27me3的含量降低。但是，减少的PHF1水平也会导致H3K27me3的整体水平下降。值得注意的是，在上调的HoxA基因座上，H3K27me3的水平降低，而H3K27me2的水平升高。与此相一致的是，添加PHF1可以在体外特异性刺激Ezh2催化H3K27me3的能力，而不是H3K27me1 / H3K27me2的能力。我们得出的结论是，PHF1调节Ezh2的活性，有利于抑制性H3K27me3标记。因此，我们建议PHF1是PcG介导的基因阻遏的决定因素。

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