[HTML][HTML] The rate of glycolysis quantitatively mediates specific histone acetylation sites

AA Cluntun, H Huang, L Dai, X Liu, Y Zhao… - Cancer & …, 2015 - Springer
Cancer & metabolism, 2015Springer
Background Glucose 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. Results Here, 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 …
Background
Glucose 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.
Results
Here, 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.
Conclusions
We 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.
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