Functional connection between histone acetyltransferase Gcn5p and methyltransferase Hmt1p
Functional connection between histone acetyltransferase Gcn5p and methyltransferase Hmt1p
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DOI：
10.1016/j.bbagrm.2009.03.004
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发表时间：
2009-05-01
影响因子：
4.7
通讯作者：
Guo, Dawei
中科院分区：
文献类型：
--
作者：
Kuo, Min-Hao;Xu, Xin-Jing;Guo, Dawei
组蛋白乙酰化和甲基化与多种核活动有关，最显著的是转录调控。这两种修饰之间的协同和拮抗关系在不同的系统中都有报道。在这里，我们证明了发芽酵母组蛋白H4精氨酸3(R3)甲基转移酶Hmt1p与乙酰化组蛋白H3和H4结合，重要的是，乙酰化H4是Hmt1p更好的甲基化底物。动力学研究表明，组蛋白H4的四个可乙酰化赖氨酸残基中的任何一个发生乙酰化都会导致更有效的甲基化。其中K8乙酰化对降低K-M的作用最强，与观察到的乙酰化刺激的相互作用一致。在体内，hmt1 Delta细胞修复了GCN5缺失引起的转录缺陷，表明Gcn5p的功能之一是中和Hmt1p的负效应。在选择性的组蛋白和gcn5突变背景下，将K8或R3突变为丙氨酸会导致类似的生长缺陷，这表明这两个残基在相同的途径上发挥着最佳营养生长的作用。综上所述，这些结果揭示了组蛋白乙酰化、甲基化和两种负责酶Gcn5p和Hmt1p之间的功能联系。(C)2009爱思唯尔B.V.保留所有权利。
Histone acetylation and methylation are linked to a variety of nuclear activities, most notably transcriptional regulation. Both synergistic and antagonistic relationships between these two modifications have been reported in different systems. Here we show that the budding yeast histone H4 arginine 3 (R3) methyltransferase Hmt1p binds acetylated histones H3 and H4, and importantly, that acetylated H4 is a significantly better methylation substrate for Hmt1p. Kinetic studies show that acetylation at any of the four acetylatable lysine residues of histone H4 results in more efficient methylation. Among the four, K8 acetylation imposes the strongest effect on reducing K-M, consistent with the observed acetylation-stimulated interaction. In vivo, hmt1 Delta cells rescue the transcriptional defect caused by GCN5 deletion, indicating that one of the functions of Gcn5p is to neutralize the negative effect of Hmt1p. Mutating either K8 or R3 to alanine causes similar growth defects in selective histone and gcn5 mutant background, suggesting that these two residues function in the same pathway for optimal vegetative growth. Together, these results reveal a functional connection between histone acetylation, methylation, and two of the responsible enzymes, Gcn5p and Hmt1p. (C) 2009 Elsevier B.V. All rights reserved.