Glucose metabolism induces mono-ubiquitination of histone H2B in mammalian cells.
Histone modifications play an important role in transcriptional regulation and are intimately involved in important biological and disease processes. Despite their functional significance, whether and how extracellular signals modulate histone modifications are not well defined. Using mono-ubiquitination of histone H2B as a model system, we have previously shown that mono-ubiquitination of histone H2B is induced by glucose through glycolysis in budding yeast Saccharomyces cerevisiae. Because histones are well conserved proteins among eukaryotes and glycolysis is the most conserved metabolic pathway, we reasoned that the glucose-glycolysis-uH2B signal pathway originally discovered in yeast may be conserved in human cells. Using cultured human glioma cells as a model, we show in this report that extracellular media modulated global levels of mono-ubiquitination of histone H2B at K120 (uH2B). Nutrient deprivation removed the ubiquitin moiety of uH2B. Glucose-containing media induced uH2B in the cells while media lacking glucose had no effect on the induction of uH2B, suggesting that glucose was required for inducing uH2B in the cells. In contrast, non-metabolic glucose analogs were defective in inducing uH2B, suggesting that glucose metabolism was required for glucose-induced mono-ubiquitination in the cultured glioma cells. Moreover, shRNA knockdown of PKM2, an essential enzyme for glycolysis in malignant tumors, inhibited mono-ubiquitination of histone H2B in these cells. Taken together, our previous and current results demonstrate that the novel glucose-glycolysis-uH2B signal pathway is well conserved from yeast to mammalian cells, providing an evolutionarily-conserved regulatory mechanism of histone modifications.
Department of Drug Development, Nevada Cancer Institute, 1 Breakthrough Way, Las Vegas, NV 89135, USA.
Zhen
Z
Gao
C Wilson
CW
Xu
D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006019:Glycolysis; D006657:Histones / Q000378:metabolism*; D006801:Humans; D054875:Ubiquitination
D006657:Histones; D005947:Glucose