Glucose Starvation Induces a Switch in the Histone Acetylome for Activation of Gluconeogenic and Fat Metabolism Genes [RNA-seq]

Acetyl-CoA is a key intermediate in metabolism situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables gene expression to be coordinated with metabolic state. Previous studies have linked abundant histone acetylation to activation of genes involved in cell growth or tumorigenesis. However, under glucose starvation, the extent to which histone acetylation is important for gene expression remains poorly understood. Here, we use a yeast starvation model to unravel a dramatic alteration in global occupancy of histone acetylation following carbon starvation. We observe a shift in the location of histone acetylation marks from growth-promoting genes to genes required for gluconeogenesis and fat metabolism. This switch is mediated by both the histone deacetylase Rpd3 and the Gcn5p/SAGA acetyltransferase. Our findings reveal a striking specificity for histone acetylation in promoting pathways that generate acetyl-CoA for oxidation when intracellular acetyl-CoA is limiting .乙酰辅酶A（Acetyl-CoA）是代谢过程中的关键中间产物，坐落于众多代谢通路的交汇节点。组蛋白乙酰化（histone acetylation）对乙酰辅酶A的依赖，使得基因表达能够与细胞代谢状态实现协调统一。既往研究已将高水平组蛋白乙酰化与细胞生长或肿瘤发生相关基因的激活效应建立关联。然而，在葡萄糖饥饿条件下，组蛋白乙酰化对基因表达的重要性程度仍未得到充分阐释。本研究借助酵母饥饿模型，揭示了碳饥饿后组蛋白乙酰化的全基因组分布水平发生的剧烈改变。我们观察到，组蛋白乙酰化修饰的位点从促生长基因转向糖异生（gluconeogenesis）与脂肪代谢所需的功能基因。这一调控转变由组蛋白去乙酰化酶（histone deacetylase）Rpd3以及Gcn5p/SAGA乙酰转移酶共同介导。本研究结果揭示了一项显著的特异性机制：当细胞内乙酰辅酶A匮乏时，组蛋白乙酰化会优先促进那些生成乙酰辅酶A以进行氧化的代谢通路。