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首页> 外文期刊>Epigenetics & Chromatin >The fungus Neurospora crassa displays telomeric silencing mediated by multiple sirtuins and by methylation of histone H3 lysine 9
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The fungus Neurospora crassa displays telomeric silencing mediated by multiple sirtuins and by methylation of histone H3 lysine 9

机译：真菌Neurospora crassa表现出由多种沉默调节蛋白和组蛋白H3赖氨酸的甲基化介导的端粒沉默9

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Background Silencing of genes inserted near telomeres provides a model to investigate the function of heterochromatin. We initiated a study of telomeric silencing in Neurospora crassa, a fungus that sports DNA methylation, unlike most other organisms in which telomeric silencing has been characterized. Results The selectable marker, hph, was inserted at the subtelomere of Linkage Group VR in an nst-1 (neurospora sir two-1) mutant and was silenced when nst-1 function was restored. We show that NST-1 is an H4-specific histone deacetylase. A second marker, bar, tested at two other subtelomeres, was similarly sensitive to nst-1 function. Mutation of three additional SIR2 homologues, nst-2, nst-3 and nst-5, partially relieved silencing. Two genes showed stronger effects: dim-5, which encodes a histone H3 K9 methyltransferase and hpo, which encodes heterochromatin protein-1. Subtelomeres showed variable, but generally low, levels of DNA methylation. Elimination of DNA methylation caused partial derepression of one telomeric marker. Characterization of histone modifications at subtelomeric regions revealed H3 trimethyl-K9, H3 trimethyl-K27, and H4 trimethyl-K20 enrichment. These modifications were slightly reduced when telomeric silencing was compromised. In contrast, acetylation of histones H3 and H4 increased. Conclusion We demonstrate the presence of telomeric silencing in Neurospora and show a dependence on histone deacetylases and methylation of histone H3 lysine 9. Our studies also reveal silencing functions for DIM-5 and HP1 that appear independent of their role in de novo DNA methylation.
机译：背景端粒附近插入的基因的沉默为研究异染色质的功能提供了一个模型。我们启动了神经孢子虫（Neurospora crassa）中端粒沉默的研究，Neurospora crassa是一种具有DNA甲基化功能的真菌，与大多数其他表征端粒沉默的生物不同。结果选择标记hph插入nst-1（神经孢子2-1突变体）突变体Linkage组VR的亚端粒中，并在恢复nst-1功能时被沉默。我们显示NST-1是一种H4特异性组蛋白脱乙酰基酶。在其他两个亚端粒处测试的第二个标记物bar对nst-1功能也同样敏感。突变另外三个SIR2同源物nst-2，nst-3和nst-5，部分缓解了沉默。两个基因显示出更强的作用：dim-5和hpo分别编码组蛋白H3 K9甲基转移酶和hpo，hepo编码异染色质蛋白-1。亚端粒显示出可变但通常较低的DNA甲基化水平。 DNA甲基化的消除引起一种端粒标记的部分抑制。在亚端粒区域的组蛋白修饰的表征揭示了H3三甲基K9，H3三甲基K27和H4三甲基K20富集。当端粒沉默受到损害时，这些修饰会稍微减少。相反，组蛋白H3和H4的乙酰化增加。结论我们证明了神经孢菌中端粒沉默的存在，并显示了对组蛋白脱乙酰酶和组蛋白H3赖氨酸9甲基化的依赖性。我们的研究还揭示了DIM-5和HP1的沉默功能，这些功能独立于它们在DNA甲基化中的作用。

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