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异染色质蛋白1对粗糙脉孢菌中的DNA甲基化至关重要。

HP1 is essential for DNA methylation in neurospora.

作者信息

Freitag Michael, Hickey Patrick C, Khlafallah Tamir K, Read Nick D, Selker Eric U

机构信息

Department of Biology and Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 USA.

出版信息

Mol Cell. 2004 Feb 13;13(3):427-34. doi: 10.1016/s1097-2765(04)00024-3.

Abstract

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.

摘要

胞嘧啶甲基化可使哺乳动物、植物和一些真菌中的转座元件及特定细胞基因沉默。最近的研究发现揭示了DNA甲基化与特殊浓缩染色质(“异染色质”)特征之间的机制联系。在粗糙脉孢菌中,DNA甲基化依赖于DIM-5对组蛋白H3赖氨酸9位点的三甲基化作用。异染色质蛋白HP1在体外可结合甲基化的赖氨酸9。因此,我们研究了粗糙脉孢菌HP1同源物读取甲基化赖氨酸9标记以指示DNA甲基化的可能性。我们鉴定出一种HP1同源物,并表明它对DNA甲基化至关重要,定位于异染色质位点,且这种定位依赖于DIM-5的催化活性。我们得出结论,HP1作为甲基化的H3赖氨酸9与DNA甲基化机制之间的衔接子。与缺乏DNA甲基转移酶的突变体不同,HP1基因hpo有缺陷的突变体表现出严重的生长缺陷,这表明HP1除了DNA甲基化外,在其他过程中也必不可少。

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