HP1 is essential for DNA methylation in Neurospora
HP1 is essential for DNA methylation in Neurospora
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DOI：
10.1016/s1097-2765(04)00024-3
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发表时间：
2004-02-13
期刊：
影响因子：
16
通讯作者：
Selker, EU
中科院分区：
文献类型：
--
作者：
Freitag, M;Hickey, PC;Selker, EU
胞嘧啶的甲基化使转座因子和哺乳动物、植物和某些真菌中选定的细胞基因沉默。最近的发现揭示了DNA甲基化和特化的浓缩染色质（“异染色质”）特征之间的机械联系。在粗糙脉孢菌中，DNA甲基化依赖于DIM-5对组蛋白H3中Lys 9的三甲基化。异染色质蛋白HP 1在体外结合甲基化Lys 9。因此，我们研究了脉孢菌HP 1同源物读取甲基-Lys 9标记以发出DNA甲基化信号的可能性。我们确定了一个HP 1同源物，并表明它是DNA甲基化所必需的，是本地化的异染色质焦点，这种定位是依赖于DIM-5的催化活性。我们的结论是，HP 1作为一个接头之间的甲基化H3 Lys 9和DNA甲基化机器。与缺乏DNA甲基转移酶的突变体不同，HP 1基因hpo缺陷的突变体表现出严重的生长缺陷，这表明HP 1是DNA甲基化以外的过程所必需的。
Methylation of cytosines silences transposable elements and selected cellular genes in mammals, plants, and some fungi. Recent findings have revealed mechanistic connections between DNA methylation and features of specialized condensed chromatin, "heterochromatin." In Neurospora crassa, DNA methylation depends on trimethylation of Lys9 in histone H3 by DIM-5. Heterochromatin protein HP1 binds methylated Lys9 in vitro. We therefore investigated the possibility that a Neurospora HP1 homolog reads the methyl-Lys9 mark to signal DNA methylation. We identified an HP1 homolog and showed that it is essential for DNA methylation, is localized to heterochromatic foci, and that this localization is dependent on the catalytic activity of DIM-5. We conclude that HP1 serves as an adaptor between methylated H3 Lys9 and the DNA methylation machinery. Unlike mutants that lack DNA methyltransferase, mutants with defects in the HP1 gene hpo exhibit severe growth defects, suggesting that HP1 is required for processes besides DNA methylation.