Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14
Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14
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DOI：
10.1016/s1097-2765(00)80257-9
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发表时间：
2000-06-01
期刊：
影响因子：
16
通讯作者：
Berger, SL
中科院分区：
文献类型：
--
作者：
Lo, WS;Trievel, RC;Berger, SL
核心组蛋白的氨基末端存在多个共价修饰，但它们之间是否存在关系尚不清楚。我们研究了组蛋白H3中丝氨酸10磷酸化和赖氨酸14乙酰化之间的关系，并发现，在体外，几种HAT酶显示对具有磷酸化-Ser-10的H3肽的活性增加。Ser-10磷酸化对yGcn 5乙酰化的增强作用通过丙氨酸取代精氨酸164 [Gcn 5（R164 A）]而丧失，精氨酸164是三元tGcn 5/CoA/组蛋白H3复合物结构中接近Ser-10的残基。Gcn 5（R164 A）在Gcn 5依赖性启动子的一个子集上具有降低的体内活性，并且引人注目的是，组蛋白H3尾部中丝氨酸10被丙氨酸取代也损害了该相同基因子集的转录。这些观察结果表明，转录调控发生的多个机械连接的组蛋白的共价修饰。
Multiple covalent modifications exist in the amino-terminal tails of core histones, but whether a relationship exists between them is unknown. We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes displayed increased activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same subset of genes was also impaired by substitution of serine 10 to alanine in the histone H3 tail. These observations suggest that transcriptional regulation occurs by multiple mechanistically linked covalent modifications of histones.