BackgroundGlucose metabolism links metabolic status to protein acetylation. However, it remains poorly understood to what extent do features of glucose metabolism contribute to protein acetylation and whether the process can be dynamically and quantitatively regulated by differing rates of glycolysis.ResultsHere, we show that titratable rates of glycolysis with corresponding changes in the levels of glycolytic intermediates result in a graded remodeling of a bulk of the metabolome and resulted in gradual changes in total histone acetylation levels. Dynamic histone acetylation levels were found and most strongly correlated with acetyl coenzyme A (ac-CoA) levels and inversely associated with the ratio of ac-CoA to free CoA. A multiplexed stable isotopic labeling by amino acids in cell culture (SILAC)-based proteomics approach revealed that the levels of half of identified histone acetylation sites as well as other lysine acylation modifications are tuned by the rate of glycolysis demonstrating that glycolytic rate affects specific acylation sites.ConclusionsWe demonstrate that histone acylation is directly sensed by glucose flux in a titratable, dose-dependent manner that is modulated by glycolytic flux and that a possible function of the Warburg Effect, a metabolic state observed in cancers with enhanced glucose metabolism, is to confer specific signaling effects on cells.

中文翻译：

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糖酵解速率定量介导特定组蛋白乙酰化位点

背景葡萄糖代谢将代谢状态与蛋白质乙酰化联系起来。然而，人们对葡萄糖代谢的特征在多大程度上有助于蛋白质乙酰化以及该过程是否可以通过不同的糖酵解速率进行动态和定量调节仍然知之甚少。糖酵解中间体导致大部分代谢组的分级重塑，并导致总组蛋白乙酰化水平的逐渐变化。发现动态组蛋白乙酰化水平与乙酰辅酶 A (ac-CoA) 水平最密切相关，并与 ac-CoA 与游离 CoA 的比率呈负相关。