PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis
PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis
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PHF8 是一种组蛋白 H3K9me2 去甲基化酶，调节 rRNA 合成
DOI：
10.1038/cr.2010.75
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发表时间：
2010-07-01
期刊：
影响因子：
44.1
通讯作者：
Chen, Charlie Degui
中科院分区：
文献类型：
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作者：
Zhu, Ziqi;Wang, Yanru;Chen, Charlie Degui
组蛋白H3赖氨酸9（H3K9me2）的二甲基化是与转录抑制相关的重要表观遗传标记。在这里，我们确定PHF8，一个JmjC结构域的蛋白质，作为一个组蛋白去甲基化酶特异性抑制标记。重组全长野生型蛋白可以从H3K9me2中去除甲基化，但保守的组氨酸突变为丙氨酸H247A废除了去甲基化酶活性。B23染色共定位过表达的外源性PHF 8。内源性PHF8也与B23和fibrillarin共定位，这两种成熟的核仁蛋白，表明PHF8定位于核仁中，并可能调节rRNA转录。事实上，PHF8结合到rDNA基因的启动子区。敲低PHF8基因可降低rRNA的表达，而过表达则导致rRNA转录本的上调。与此同时，H3K9me2水平升高的rDNA基因的启动子区域中的PHF8敲除细胞和野生型，但不是催化失活的H247A突变体PHF8过表达时显着降低。因此，我们的研究确定了H3K9me2的组蛋白去甲基化酶，调节rRNA转录。
Dimethylation of histone H3 lysine 9 (H3K9me2) is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.