Sir2 is required for Clr4 to initiate centromeric heterochromatin assembly in fission yeast.
Sir2 is required for Clr4 to initiate centromeric heterochromatin assembly in fission yeast.
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DOI：
10.1038/emboj.2013.143
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发表时间：
2013-08-28
期刊：
影响因子：
11.4
通讯作者：
Partridge, Janet F.
中科院分区：
文献类型：
--
作者：
Alper, Benjamin J.;Job, Godwin;Yadav, Rajesh K.;Shanker, Sreenath;Lowe, Brandon R.;Partridge, Janet F.
裂殖酵母中的异染色质组装依赖于Clr 4组蛋白甲基转移酶，其靶向H3K9。我们发现，组蛋白去乙酰化酶Sir2是所需的Clr4活性在端粒，但与Clr3组蛋白去乙酰化酶冗余的行为，以维持着丝粒异染色质。然而，在从头着丝粒异染色质组装过程中，Sir2对Clr4功能至关重要。我们确定了Sir2的新靶点，并测试了它们的去乙酰化是否是Clr4介导的异染色质建立所必需的。Sir2优先使H4K16Ac和H3K4Ac脱乙酰化，但这些残基的突变以模拟乙酰化并不能阻止Clr4介导的异染色质建立。Sir2也使H3K9Ac和H3K14Ac脱乙酰基。携带H3K9或H3K14突变的菌株表现出异染色质缺陷。H3K9突变阻断Clr4功能，但H3K14突变影响异染色质的原因尚不清楚。在这里，我们证明，招募Clr4着丝粒被阻断突变H3K14。我们认为，Sir2去乙酰化H3K14靶向Clr4的着丝粒。此外，我们证明了Sir2对于RNAi缺陷细胞中H3K9me2的从头积累至关重要。这些分析将Sir2和H3K14脱乙酰化置于异染色质组装期间Clr4募集的上游。
Heterochromatin assembly in fission yeast depends on the Clr4 histone methyltransferase, which targets H3K9. We show that the histone deacetylase Sir2 is required for Clr4 activity at telomeres, but acts redundantly with Clr3 histone deacetylase to maintain centromeric heterochromatin. However, Sir2 is critical for Clr4 function during de novo centromeric heterochromatin assembly. We identified new targets of Sir2 and tested if their deacetylation is necessary for Clr4-mediated heterochromatin establishment. Sir2 preferentially deacetylates H4K16Ac and H3K4Ac, but mutation of these residues to mimic acetylation did not prevent Clr4-mediated heterochromatin establishment. Sir2 also deacetylates H3K9Ac and H3K14Ac. Strains bearing H3K9 or H3K14 mutations exhibit heterochromatin defects. H3K9 mutation blocks Clr4 function, but why H3K14 mutation impacts heterochromatin was not known. Here, we demonstrate that recruitment of Clr4 to centromeres is blocked by mutation of H3K14. We suggest that Sir2 deacetylates H3K14 to target Clr4 to centromeres. Further, we demonstrate that Sir2 is critical for de novo accumulation of H3K9me2 in RNAi-deficient cells. These analyses place Sir2 and H3K14 deacetylation upstream of Clr4 recruitment during heterochromatin assembly.
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