Cheung P, Tanner K G, Cheung W L, Sassone-Corsi P, Denu J M, Allis C D
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville 22908, USA.
Mol Cell. 2000 Jun;5(6):905-15. doi: 10.1016/s1097-2765(00)80256-7.
Histone acetylation and phosphorylation have separately been suggested to affect chromatin structure and gene expression. Here we report that these two modifications are synergistic. Stimulation of mammalian cells by epidermal growth factor (EGF) results in rapid and sequential phosphorylation and acetylation of H3, and these dimodified H3 molecules are preferentially associated with the EGF-activated c-fos promoter in a MAP kinase-dependent manner. In addition, the prototypical histone acetyltransferase Gcn5 displays an up to 10-fold preference for phosphorylated (Ser-10) H3 over nonphosphorylated H3 as substrate in vitro, suggesting that H3 phosphorylation can affect the efficiency of subsequent acetylation reactions. Together, these results illustrate how the addition of multiple histone modifications may be coupled during the process of gene expression.
组蛋白乙酰化和磷酸化分别被认为会影响染色质结构和基因表达。在此我们报告这两种修饰具有协同作用。表皮生长因子（EGF）刺激哺乳动物细胞会导致H3快速且依次发生磷酸化和乙酰化，并且这些双修饰的H3分子以丝裂原活化蛋白激酶（MAP激酶）依赖的方式优先与EGF激活的c-fos启动子相关联。此外，典型的组蛋白乙酰转移酶Gcn5在体外对磷酸化（Ser-10）H3作为底物的偏好性比对非磷酸化H3高10倍，这表明H3磷酸化可影响后续乙酰化反应的效率。这些结果共同说明了在基因表达过程中多种组蛋白修饰的添加是如何相互关联的。
