Multiple roles for Saccharomyces cerevisiae histone H2A in telomere position effect, Spt phenotypes and double-strand-break repair.
Multiple roles for Saccharomyces cerevisiae histone H2A in telomere position effect, Spt phenotypes and double-strand-break repair.
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酿酒酵母组蛋白 H2A 在端粒位置效应、Spt 表型和双链断裂修复中的多重作用。
DOI：
10.1093/genetics/164.1.47
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发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Lustig,ArthurJ
中科院分区：
文献类型：
--
作者：
Wyatt,HollyR;Liaw,Hungjiun;Green,GeorgeR;Lustig,ArthurJ
端粒位置对转录的影响（TPE或端粒沉默）通过非组蛋白沉默因子与端粒的结合而成核，并通过沉默因子与特异性修饰的组蛋白H3和H4的结合而在亚端粒区域中传播。然而，组蛋白H2A在TPE中的功能尚不清楚。我们发现H2A的氨基或羧基尾部的缺失显著降低TPE。我们确定了TPE的野生型效率所必需的四个H2A修饰位点。这些“hta1tpe”等位基因也作为LYS2的δ插入等位基因的抑制子，表明两个基因座的染色质结构具有共同的元件。有趣的是，我们观察到等位基因对的组合效应，这表明氨基末端尾中相互依赖的乙酰化和脱乙酰化事件以及羧基末端尾中多个磷酸化残基之间的调节回路。分别用低浓度和高浓度的博莱霉素处理后，观察到mosthta1 tpe等位基因的沉默和活力下降，博莱霉素形成双链断裂（DSB）。在缺乏DSB和端粒结合蛋白yKu70的情况下，hta1等位基因的博莱霉素敏感性进一步增强。我们还提供的数据表明存在的yKu依赖性组蛋白H2A功能的TPE。这些数据表明，H2A的氨基末端和羧基末端尾对于yKu介导的TPE和DSB修复的野生型水平是必需的。
Telomere position effects on transcription (TPE, or telomeric silencing) are nucleated by association of nonhistone silencing factors with the telomere and propagated in subtelomeric regions through association of silencing factors with the specifically modified histones H3 and H4. However, the function of histone H2A in TPE is unknown. We found that deletion of either the amino or the carboxyltails of H2A substantially reduces TPE. We identified four H2A modification sites necessary for wild-type efficiency of TPE. These “hta1tpe” alleles also act as suppressors of a δ insertion allele ofLYS2, suggesting shared elements of chromatin structure at both loci. Interestingly, we observed combinatorial effects of allele pairs, suggesting both interdependent acetylation and deacetylation events in the amino-terminal tail and a regulatory circuit between multiple phosphorylated residues in the carboxyl-terminal tail. Decreases in silencing and viability are observed in mosthta1tpealleles after treatment with low and high concentrations, respectively, of bleomycin, which forms double-strand breaks (DSBs). In the absence of the DSB and telomere-binding protein yKu70, the bleomycin sensitivity ofhta1tpealleles is further enhanced. We also provide data suggesting the presence of a yKu-dependent histone H2A function in TPE. These data indicate that the amino- and carboxyl-terminal tails of H2A are essential for wild-type levels of yKu-mediated TPE and DSB repair.