Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae
Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.115.175885
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发表时间：
2015-07-01
期刊：
影响因子：
3.3
通讯作者：
Wyrick, John J.
中科院分区：
文献类型：
--
作者：
Hodges, Amelia J.;Gallegos, Isaura J.;Wyrick, John J.
将DNA结合到组蛋白八聚体的分子间接触的一个关键特征是在每个超螺旋位置插入DNA小沟的一系列组蛋白精氨酸残基，其中小沟面向组蛋白八聚体。这些“链轮”精氨酸残基之一，组蛋白H4 R45，显著影响体内染色质结构，并且当在酿酒酵母（芽殖酵母）中突变为丙氨酸或半胱氨酸时是致命的。然而，剩余的链轮精氨酸残基（H3 R63、H3 R83、H2 A R43、H2 B R36、H2 A R78、H3 R49）在染色质结构和其他细胞过程中的作用尚未得到充分表征。我们已经在这些组蛋白残基中的每一个单独或组合引入酵母细胞时的遗传特征突变。我们发现，对精氨酸残基结合DNA相邻的DNA出口/进入位点的核小体是致命的酵母突变时，在组合和组蛋白占用的缺陷。此外，单个残基的突变损害UV诱导的DNA损伤的修复，并影响基因表达和隐蔽转录。这项研究揭示了DNA结合的位置和结构模式如何影响每个组蛋白链轮精氨酸残基的生物学功能的简单规则。
A critical feature of the intermolecular contacts that bind DNA to the histone octamer is the series of histone arginine residues that insert into the DNA minor groove at each superhelical location where the minor groove faces the histone octamer. One of these "sprocket" arginine residues, histone H4 R45, significantly affects chromatin structure in vivo and is lethal when mutated to alanine or cysteine in Saccharomyces cerevisiae (budding yeast). However, the roles of the remaining sprocket arginine residues (H3 R63, H3 R83, H2A R43, H2B R36, H2A R78, H3 R49) in chromatin structure and other cellular processes have not been well characterized. We have genetically characterized mutations in each of these histone residues when introduced either singly or in combination to yeast cells. We find that pairs of arginine residues that bind DNA adjacent to the DNA exit/entry sites in the nucleosome are lethal in yeast when mutated in combination and cause a defect in histone occupancy. Furthermore, mutations in individual residues compromise repair of UV-induced DNA lesions and affect gene expression and cryptic transcription. This study reveals simple rules for how the location and structural mode of DNA binding influence the biological function of each histone sprocket arginine residue.