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 . Overall design: RNA-seq to compare between two different conditions and three different strains.

乙酰辅酶A (Acetyl-CoA) 是代谢过程中的关键中间产物，处于多条代谢通路的交汇节点。组蛋白乙酰化依赖于乙酰辅酶A，这使得基因表达能够与细胞代谢状态实现协调统一。既往研究已证实，高水平的组蛋白乙酰化与细胞生长或肿瘤发生相关基因的激活密切相关。然而，在葡萄糖饥饿条件下，组蛋白乙酰化对基因表达的具体重要性仍不甚明确。本研究采用酵母饥饿模型，解析了碳饥饿后组蛋白乙酰化的全基因组占据模式发生的显著重塑。我们观察到，组蛋白乙酰化标记的分布位置从促生长基因转向糖异生与脂肪代谢所需的基因。这一转换由组蛋白去乙酰化酶Rpd3以及Gcn5p/SAGA乙酰转移酶共同介导。本研究揭示，当细胞内乙酰辅酶A水平受限之时，组蛋白乙酰化对促进生成可用于氧化供能的乙酰辅酶A的通路具有显著的特异性调控作用。整体实验设计：通过RNA测序对两种不同培养条件及三种不同酵母菌株进行比较分析。