Abstract
Histone modifications have emerged to be a major regulatory mechanism for gene expression (1-4). However, it is not clear how histone modifications are physiologically regulated. Here, we show that mono-ubiquitinated H2B at lysine 123 (uH2B) in the yeast (Saccharomyces cerevisiae) is present in exponential phase and absent in stationary phase. A wide array of carbohydrates or sugars, including glucose, fructose, mannose, and sucrose, are capable of inducing uH2B in stationary phase yeast. In contrast, non-metabolic glucose analogs are defective in inducing uH2B. Furthermore, uH2B induction is inhibited by iodoacetate, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase in glycolysis. Moreover, uH2B induction is markedly impaired in yeast mutants, in which glycolytic genes are deleted. These data indicate that glycolysis is required for the carbohydrate-induced mono-ubiquitination of H2B at lysine 123. Therefore, our study reveals a novel paradigm of metabolic regulation of histone modifications.
Highlights
Histone modifications have emerged to be a major regulatory mechanism for gene expression [1,2,3,4]
In the budding yeast (Saccharomyces cerevisiae), histone H2B is mono-ubiquitinated at lysine 123 [8], which is required for H3 methylation at lysines 4 and 79, a phenomenon termed trans-tail regulation of histone modification (9 –11). ubiquitinated H2B at lysine 123 (uH2B) is mediated by Bre-1, a ubiquitin E3 ligase, and regulated by Rad6, Lge1, Rtf1, and Ubp8 [8, 12,13,14,15,16]. uH2B plays a role in gene silencing in telomeres [9, 17] and in controlling cell size control [12]
We further found that uH2B was absent in stationary phase Y96 that was cultured in YPD (1% yeast extract, 2% peptone, and 2% glucose) for 7 days (Fig. 1A, lane 3)
Summary
Histone modifications have emerged to be a major regulatory mechanism for gene expression [1,2,3,4]. We show that mono-ubiquitinated H2B at lysine 123 (uH2B) in the yeast (Saccharomyces cerevisiae) is present in exponential phase and absent in stationary phase. A wide array of carbohydrates or sugars, including glucose, fructose, mannose, and sucrose, are capable of inducing uH2B in stationary phase yeast.
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