Lo W S, Trievel R C, Rojas J R, Duggan L, Hsu J Y, Allis C D, Marmorstein R, Berger S L
Molecular Genetics Program, Wistar Institute, Philadelphia, Pennsylvania 19024, USA.
Mol Cell. 2000 Jun;5(6):917-26. doi: 10.1016/s1097-2765(00)80257-9.
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.
核心组蛋白的氨基末端尾巴存在多种共价修饰，但它们之间是否存在关联尚不清楚。我们研究了组蛋白H3中丝氨酸10磷酸化与赖氨酸14乙酰化之间的关系，发现在体外，几种组蛋白乙酰转移酶（HAT）对含有磷酸化丝氨酸10的H3肽表现出更高的活性。通过将丙氨酸替代精氨酸164 [Gcn5(R164A)]，丝氨酸10磷酸化对yGcn5介导的乙酰化的这种增强作用消失了，精氨酸164是三元tGcn5/辅酶A/组蛋白H3复合物结构中靠近丝氨酸10的一个残基。Gcn5(R164A)在体内对一部分Gcn5依赖的启动子活性降低，而且，引人注目的是，通过将组蛋白H3尾巴中的丝氨酸10替换为丙氨酸，同一组基因的转录也受到了损害。这些观察结果表明，转录调控是通过组蛋白多种机制上相互关联的共价修饰发生的。
