A core nucleosome surface crucial for transcriptional silencing
A core nucleosome surface crucial for transcriptional silencing
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DOI：
10.1038/ng982
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发表时间：
2002-10-01
期刊：
影响因子：
30.8
通讯作者：
Boeke, JD
中科院分区：
文献类型：
--
作者：
Park, JH;Cosgrove, MS;Boeke, JD
酵母中的转录沉默为分析异染色质的形成和维持提供了一个遗传上容易处理的系统，异染色质是一种存在于所有生物体中的转录抑制染色质结构。核小体构成染色质的中心结构，由组蛋白H_2A、H_2B、H_3和H_4两条链组成。核小体的结构由一个中央球状核心组成，周围环绕着向外突出的氨基末端组蛋白尾巴。我们证明，在酵母中沉默需要组装的核小体核心的特定表面。该表面位于H3/H4组蛋白折叠基序上，含有位于核小体表面和与DNA相互作用的相邻表面上的氨基酸侧链。从所有三种沉默形式(rDNA、端粒和沉默交配位点沉默)都被消除的突变体中鉴定出的侧链，集中在组蛋白H3的Lys79周围，这是一种由酵母Dot1蛋白(1，2)甲基化的残基。此外，编码H3(HHT1和HHT2)和H4(HHF1和HHF2)的基因突变映射到空间相邻的氨基酸残基上，明显影响了三种形式的沉默，表明特定的相互作用介导了每种形式的沉默。我们发现的几个突变与以前发现的一系列突变中的那些相似，这些突变影响着核小体核心其他地方的一个独特的组蛋白折叠基序。这两个簇缓解了不同形式的转录抑制(沉默与缺乏Swi/SNF染色质重塑活性导致的抑制)。
Transcriptional silencing in yeast provides a genetically tractable system for analyzing the formation and maintenance of heterochromatin, a transcriptionally repressive chromatin structure found in all organisms. The nucleosome constitutes the central structure of chromatin and comprises two chains each of histones H2A, H2B, H3 and H4. The structure of the nucleosome consists of a central globular core surrounded by outwardly protruding amino-terminal histone tails. We show that a specific surface of the assembled nucleosome core is required for silencing in yeast. This surface is located at a H3/H4 histone-fold motif and contains amino-acid side chains located on the nucleosome disk surface and on an adjacent surface that interacts with DNA. The side chains, identified from mutants in which all three forms of silencing (rDNA, telomere and silent mating locus silencing) are eliminated, are centered around Lys79 of histone H3, a residue methylated by the yeast Dot1 protein(1,2). Moreover, mutations in the genes encoding H3 (HHT1 and HHT2) and H4 (HHF1 and HHF2) mapping to spatially adjacent amino-acid residues affected the three forms of silencing distinctly, suggesting that specific interactions mediate each form of silencing. Several of the mutations that we identified resemble those in a cluster of previously identified mutations affecting a distinct histone-fold motif elsewhere in the nucleosome core. These two clusters relieve distinct forms of transcriptional repression (silencing versus repression resulting from lack of Swi/Snf chromatin remodeling activity).