Mutations in the nucleosome core enhance transcriptional silencing.
Mutations in the nucleosome core enhance transcriptional silencing.
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核小体核心的突变增强了转录沉默。
DOI：
10.1128/mcb.25.5.1846-1859.2005
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Broach,JamesR
中科院分区：
文献类型：
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作者：
Xu,EugeniaY;Bi,Xin;Holland,MichaelJ;Gottschling,DanielE;Broach,JamesR
在酵母中转录沉默需要特定的核小体修饰，部分由与修饰后的核小体结合的SIR蛋白复合体促进。最近的证据表明，组蛋白氨基末端和核小体核心区的修饰都有助于沉默。我们以前发现了组蛋白H4突变，影响核小体核心的残基，从而增强端粒的沉默。在这里，我们表明，由这些突变诱导的增强沉默增加了端粒和沉默交配型基因座处于沉默状态的细胞的比例。一个H4突变会影响一组基因的表达，这些基因的表达会因编码组蛋白变异体H2 A.Z的HTZ1的缺失而改变，这表明该突变可能会拮抗H2 A.Z掺入核小体。第二个突变导致沉默扩散到亚端粒区域，而这些区域在野生型细胞中通常不是沉默的。从机理上讲，这种突变不会显著加速沉默染色质的形成，相反，它会降低沉默状态的衰减率。我们认为，这些突变使用不同的机制来影响活跃和沉默染色质边界上的激活和抑制之间的动态相互作用。
Transcriptional silencing inSaccharomycesrequires specific nucleosome modifications promoted in part by a complex of Sir proteins that binds to the modified nucleosomes. Recent evidence suggests that modifications of both the histone amino termini and the core domain of nucleosomes contribute to silencing. We previously identified histone H4 mutations affecting residues in the core of the nucleosome that yield enhanced silencing at telomeres. Here we show that enhanced silencing induced by these mutations increases the proportion of cells in which telomeres and silent mating-type loci are in the silent state. One H4 mutation affects the expression of a subset of genes whose expression is altered by deletion ofHTZ1, which encodes the histone variant H2A.Z, suggesting that the mutation may antagonize H2A.Z incorporation into nucleosomes. A second mutation causes the spread of silencing into subtelomeric regions that are not normally silenced in wild-type cells. Mechanistically, this mutation does not significantly accelerate the formation of silent chromatin but, rather, reduces the rate of decay of the silenced state. We propose that these mutations use distinct mechanisms to affect the dynamic interplay between activation and repression at the boundary between active and silent chromatin.