Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes

Acetyl-CoA is a key intermediate situated at the intersection of many metabolic pathways. The reliance of his tone acetylation on acetyl-CoA enables the coordination of gene expression with metabolic state. Abundant acetyl-CoA has been linked to the activation of genes involved in cell growth or tumorigenesis through his tone acetylation. However, the role of histone acetylation in transcription under low levels of acetyl-CoA remains poorly understood. Here, we use a yeast starvation model to observe the dramatic alteration in the global occupancy of histone acetylation following carbon starvation; the location of histone acetylation marks shifts from growth-promoting genes to gluconeogenic and fat metabolism genes. This reallocation is mediated by both the histone deacetylase Rpd3p and the acetyltransferase Gcn5p, a component of the SAGA transcriptional coactivator. Our findings reveal an unexpected switch in the specificity of histone acetylation to promote pathways that generate acetyl-CoA for oxidation when acetyl-CoA is limiting.

Automated summary

Acetyl-CoA is a key intermediate that plays a critical role in coordinating gene expression with metabolic state. High levels of acetyl-CoA activate genes involved in cell growth or tumorigenesis through histone acetylation, but the role of histone acetylation under low levels of acetyl-CoA is not well understood. In a yeast starvation model, we observed a significant shift in the global occupancy of histone acetylation following carbon starvation. Histone acetylation marks relocate from growth-promoting genes to genes involved in gluconeogenesis and fat metabolism. This reallocation is mediated by the histone deacetylase Rpd3p and the acetyltransferase Gcn5p.