泛素连接酶组件 Cullin4 和 DDB1 对 Neurospora crassa 中的 DNA 甲基化至关重要。
Ubiquitin ligase components Cullin4 and DDB1 are essential for DNA methylation in Neurospora crassa.
机构信息
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
出版信息
J Biol Chem. 2010 Feb 12;285(7):4355-65. doi: 10.1074/jbc.M109.034710. Epub 2009 Nov 30.
DNA methylation and H3K9 trimethylation are involved in gene silencing and heterochromatin assembly in mammals and fungi. In the filamentous fungus Neurospora crassa, it has been demonstrated that H3K9 trimethylation catalyzed by histone methyltransferase DIM-5 is essential for DNA methylation. Trimethylated H3K9 is recognized by HP1, which then recruits the DNA methyltransferase DIM-2 to methylate the DNA. Here, we show that in Neurospora, ubiquitin ligase components Cullin4 and DDB1 are essential for DNA methylation. These proteins regulate DNA methylation through their effects on the trimethylation of histone H3K9. In addition, we showed that the E3 ligase activity of the Cul4-based ubiquitin ligase is required for its function in histone H3K9 trimethylation in Neurospora. Furthermore, we demonstrated that Cul4 and DDB1 are associated with the histone methyltransferase DIM-5 protein in vivo. Together, these results suggest a mechanism for DNA methylation control that may be applicable in other eukaryotic organisms.
DNA 甲基化和 H3K9 三甲基化参与哺乳动物和真菌中的基因沉默和异染色质组装。在丝状真菌粗糙脉孢菌中，已经证明由组蛋白甲基转移酶 DIM-5 催化的 H3K9 三甲基化对于 DNA 甲基化是必不可少的。三甲基化的 H3K9 被 HP1 识别，然后 HP1 招募 DNA 甲基转移酶 DIM-2 来甲基化 DNA。在这里，我们表明在粗糙脉孢菌中，泛素连接酶组件 Cullin4 和 DDB1 对于 DNA 甲基化是必不可少的。这些蛋白质通过影响组蛋白 H3K9 的三甲基化来调节 DNA 甲基化。此外，我们表明，基于 Cul4 的泛素连接酶的 E3 连接酶活性对于其在粗糙脉孢菌中组蛋白 H3K9 三甲基化中的功能是必需的。此外，我们证明 Cul4 和 DDB1 在体内与组蛋白甲基转移酶 DIM-5 蛋白相关。总之，这些结果表明了一种可能适用于其他真核生物的 DNA 甲基化控制机制。
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