Friis R Magnus N, Wu Bob P, Reinke Stacey N, Hockman Darren J, Sykes Brian D, Schultz Michael C
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Nucleic Acids Res. 2009 Jul;37(12):3969-80. doi: 10.1093/nar/gkp270. Epub 2009 Apr 30.
Little is known about what enzyme complexes or mechanisms control global lysine acetylation in the amino-terminal tails of the histones. Here, we show that glucose induces overall acetylation of H3 K9, 18, 27 and H4 K5, 8, 12 in quiescent yeast cells mainly by stimulating two KATs, Gcn5 and Esa1. Genetic and pharmacological perturbation of carbon metabolism, combined with (1)H-NMR metabolic profiling, revealed that glucose induction of KAT activity directly depends on increased glucose catabolism. Glucose-inducible Esa1 and Gcn5 activities predominantly reside in the picNuA4 and SAGA complexes, respectively, and act on chromatin by an untargeted mechanism. We conclude that direct metabolic regulation of globally acting KATs can be a potent driving force for reconfiguration of overall histone acetylation in response to a physiological cue.
关于何种酶复合物或机制控制组蛋白氨基末端尾巴上的整体赖氨酸乙酰化，人们了解甚少。在此，我们表明，葡萄糖主要通过刺激两种赖氨酸乙酰转移酶（KATs），即Gcn5和Esa1，诱导静止酵母细胞中H3的K9、18、27位点以及H4的K5、8、12位点发生整体乙酰化。碳代谢的遗传和药理学扰动，结合¹H-NMR代谢谱分析，揭示出KAT活性的葡萄糖诱导直接依赖于葡萄糖分解代谢的增加。葡萄糖诱导的Esa1和Gcn5活性分别主要存在于picNuA4和SAGA复合物中，并通过一种非靶向机制作用于染色质。我们得出结论，对全局作用的KATs进行直接代谢调控可能是响应生理信号而重新配置整体组蛋白乙酰化的强大驱动力。
