协同的DNA甲基化/组蛋白甲基化开关调节rRNA基因剂量控制和核仁显性。

A concerted DNA methylation/histone methylation switch regulates rRNA gene dosage control and nucleolar dominance.

作者信息

Lawrence Richard J, Earley Keith, Pontes Olga, Silva Manuela, Chen Z Jeffrey, Neves Nuno, Viegas Wanda, Pikaard Craig S

机构信息

Department of Biology, Washington University, St Louis, MO 63130, USA.

出版信息

Mol Cell. 2004 Feb 27;13(4):599-609. doi: 10.1016/s1097-2765(04)00064-4.

DOI:10.1016/s1097-2765(04)00064-4

PMID:14992728

Abstract

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.

摘要

真核生物调控其核糖体RNA（rRNA）基因的有效剂量，在任何时候表达的基因都不到一半。同样，表现出核仁显性的遗传杂种转录从一个亲本遗传而来的rRNA基因，但使另一亲本的基因沉默。我们表明，rRNA基因剂量控制和核仁显性利用了一种共同机制。该机制的核心是一种表观遗传开关，其中启动子胞嘧啶甲基化密度和特定组蛋白修饰的协同变化决定了rRNA基因的开启和关闭状态。关闭开关的一个关键成分是HDT1，一种植物特有的组蛋白脱乙酰酶，定位于核仁，是H3赖氨酸9去乙酰化和随后H3赖氨酸9甲基化所必需的。总体而言，这些数据支持了一个模型，即在一个自我强化的抑制循环中，胞嘧啶甲基化和组蛋白去乙酰化彼此处于上游位置。