Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa
Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa
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DOI：
10.1038/ng1143
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发表时间：
2003-05-01
期刊：
影响因子：
30.8
通讯作者：
Selker, EU
中科院分区：
文献类型：
--
作者：
Tamaru, H;Zhang, X;Selker, EU
除了用于包装核DNA外，组蛋白还以多种翻译后修饰的形式携带信息。组蛋白H3和H4的甲基化与长期表观遗传“记忆”有关(1)。在酵母和哺乳动物的可表达的常染色质中发现了组蛋白H3的Lys4的二甲基化或三甲基化（H3 Lys4）（2-4）。相反，组蛋白H3的Lys9的甲基化（H3 Lys9）与哺乳动物、酵母、果蝇和植物的大部分静止异染色质的建立和维持有关”。我们之前已经证明，粗神经孢子虫的DNA甲基化突变体dim-5（甲基化缺陷）在H3特异性组蛋白甲基转移酶的SET结构域具有无义突变，并且H3 Lys9的替换导致DNA的严重低甲基化（10）。同样，KRYPTONITE组蛋白甲基转移酶是拟南芥DNA完全甲基化所必需的（11）。采用生物化学、遗传学和免疫学等方法研究了棘草DNA甲基化的特异性标记。在这里，我们发现三甲基化的H3 Lys9，而不是二甲基化的H3 Lys9，标记了染色质区域的胞嘧啶甲基化，并且DIM-5特异性地产生了这个标记。
Besides serving to package nuclear DNA, histones carry information in the form of a diverse array of post-translational modifications. Methylation of histones H3 and H4 has been implicated in long-term epigenetic 'memory'(1). Dimethylation or trimethylation of Lys4 of histone H3 (H3 Lys4) has been found in expressible euchromatin of yeasts and mammals(2-4). In contrast, methylation of Lys9 of histone H3 (H3 Lys9) has been implicated in establishing and maintaining the largely quiescent heterochromatin of mammals, yeasts, Drosophila melanogaster and plants". we have previously shown that a DNA methylation mutant of Neurospora crassa, dim-5 (defective in methylation), has a nonsense mutation in the SET domain of an H3-specific histone methyltransferase and that substitutions of H3 Lys9 cause gross hypomethylation of DNA(10). Similarly, the KRYPTONITE histone methyltransferase is required for full DNA methylation in Arabidopsis thaliana(11). We used biochemical, genetic and immunological methods to investigate the specific mark for DNA methylation in N. crassa. Here we show that trimethylated H3 Lys9, but not dimethylated H3 Lys9, marks chromatin regions for cytosine methylation and that DIM-5 specifically creates this mark.