Functional separation of the requirements for establishment and maintenance of centromeric heterochromatin

Functional separation of the requirements for establishment and maintenance of centromeric heterochromatin
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DOI:
10.1016/j.molcel.2007.05.004
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发表时间:
2007-05-25
期刊:
影响因子:
16
通讯作者:
Noffsinger, Victoria J. P.
Noffsinger, Victoria J. P.
中科院分区:
生物学1区
文献类型:
--
作者:
Partridge, Janet F.;DeBeauchamp, Jennifer L.;Noffsinger, Victoria J. P.

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在分裂酵母中着丝粒异染色质的建立和维持需要RITS复合体。RITS由着丝粒siRNAs、染色域蛋白Chp1、ArgAerte(Ago1)和Tas3组成,将细胞RNAi途径与构成异染色质的组装结合在一起。然而,调控RITS依赖的着丝粒异染色质建立和维持的机制仍未解决。在这里,我们报告了一个不能结合Ago1的突变Tas3蛋白,它支持着丝粒异染色质的维持,但不能介导组蛋白H3赖氨酸9甲基转移酶CLR4瞬时耗尽的细胞的有效从头建立。相反,着丝粒异染色质在突变细胞中有效地组装,这些突变细胞瞬间耗尽了DICE。因此,该突变体允许对导致着丝粒异染色质建立的事件进行排序,并将组蛋白H3的赖氨酸9甲基化置于DICER功能的上游。
The establishment and maintenance of centromeric heterochromatin in fission yeast require the RITS complex. Comprised of centromeric siRNAs, the chromodomain protein Chp1, Argonaute (Ago1), and Tas3, RITS couples the cellular RNAi pathway with assembly of constitutive heterochromatin. However, the mechanisms governing RITS-dependent establishment versus maintenance of centromeric heterochromatin remain unresolved. Here, we report that a mutant Tas3 protein that cannot bind Ago1 supports the maintenance of centromeric heterochromatin but cannot mediate efficient de novo establishment from cells transiently depleted for the histone H3 lysine 9 methyltransferase Clr4. In contrast, centromeric heterochromatin efficiently assembles in mutant cells transiently depleted for dicer. This mutant therefore allows ordering of the events leading to establishment of centromeric heterochromatin and places lysine 9 methylation of histone H3 upstream of dicer function.