Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans
Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans
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秀丽隐杆线虫双特异性组蛋白去甲基化酶 ceKDM7A 对活性和抑制性组蛋白甲基化的协调调节
DOI：
10.1038/cr.2010.84
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发表时间：
2010-08-01
期刊：
影响因子：
44.1
通讯作者：
Chen, Charlie Degui
中科院分区：
文献类型：
--
作者：
Lin, Hanqing;Wang, Yiqin;Chen, Charlie Degui
H3K9me2和H3K27me2是与转录抑制相关的重要表观遗传标记，而H3K4me3与转录激活相关。研究表明，活性组蛋白甲基化和抑制性组蛋白甲基化以相互排斥的方式分布，但其潜在机制尚不清楚。在这里，我们确定了ceKDM7A，一个PHD（植物同源结构域）和JmjC结构域的蛋白质，作为一个组蛋白去甲基化酶特异性H3K9me2和H3K27me2。我们进一步证明了ceKDM7A的PHD结构域结合H3K4me3，并且H3K4me3在全基因组水平上与ceKDM7A共定位。PHD结构域与H3K4me3结合的破坏降低了体内脱甲基酶活性，并且ceKDM7A的缺失降低了其相关靶基因的表达。这些结果表明，ceKDM7A被募集到启动子以使H3K9me2和H3K27me2脱甲基化，并通过PHD结构域与H3K4me3的结合来激活基因表达。因此，我们的研究确定了一个双特异性组蛋白去甲基化酶，并提供了新的见解调控组蛋白甲基化。
H3K9me2 and H3K27me2 are important epigenetic marks associated with transcription repression, while H3K4me3 is associated with transcription activation. It has been shown that active and repressive histone methylations distribute in a mutually exclusive manner, but the underlying mechanism was poorly understood. Here we identified ceKDM7A, a PHD (plant homeodomain)-and JmjC domain-containing protein, as a histone demethylase specific for H3K9me2 and H3K27me2. We further demonstrated that the PHD domain of ceKDM7A bound H3K4me3 and H3K4me3 co-localized with ceKDM7A at the genome-wide level. Disruption of the PHD domain binding to H3K4me3 reduced the demethylase activity in vivo, and loss of ceKDM7A reduced the expression of its associated target genes. These results indicate that ceKDM7A is recruited to the promoter to demethylate H3K9me2 and H3K27me2 and activate gene expression through the binding of the PHD domain to H3K4me3. Thus, our study identifies a dual-specificity histone demethylase and provides novel insights into the regulation of histone methylation.