A concerted DNA methylation/histone methylation switch regulates rRNA gene dosage control and nucleolar dominance
A concerted DNA methylation/histone methylation switch regulates rRNA gene dosage control and nucleolar dominance
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DOI：
10.1016/s1097-2765(04)00064-4
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发表时间：
2004-02-27
期刊：
影响因子：
16
通讯作者：
Pikaard, CS
中科院分区：
文献类型：
--
作者：
Lawrence, RJ;Earley, K;Pikaard, CS
真核生物调节其核糖体RNA（rRNA）基因的有效剂量，在任何时候表达不到一半的基因。同样地，显示核仁优势的遗传杂种转录从一个亲本遗传的rRNA基因，但沉默另一个亲本。我们发现，rRNA基因的剂量控制和核仁优势利用一个共同的机制。该机制的核心是表观遗传开关，其中启动子胞嘧啶甲基化密度和特定组蛋白修饰的协调变化决定了rRNA基因的开启和关闭状态。关闭开关的一个关键组成部分是HDT1，一种植物特异性组蛋白脱乙酰酶，定位于核仁，是H3赖氨酸9脱乙酰化和随后的H3赖氨酸9甲基化所必需的。总的来说，这些数据支持一个模型，其中胞嘧啶甲基化和组蛋白去乙酰化在一个自我加强的抑制循环中彼此上游。
Eukaryotes regulate the effective dosage of their ribosomal RNA (rRNA) genes, expressing fewer than half of the genes at any one time. Likewise, genetic hybrids displaying nucleolar dominance transcribe rRNA genes inherited from one parent but silence the other parental set. We show that rRNA gene dosage control and nucleolar dominance utilize a common mechanism. Central to the mechanism is an epigenetic switch in which concerted changes in promoter cytosine methylation density and specific histone modifications dictate the on and off states of the rRNA genes. A key component of the off switch is HDT1, a plant-specific histone deacetylase that localizes to the nucleolus and is required for H3 lysine 9 deacetylation and subsequent H3 lysine 9 methylation. Collectively, the data support a model in which cytosine methylation and histone deacetylation are each upstream of one another in a self-reinforcing repression cycle.