Cell fate determination requires faithful execution of gene expression programs, which are increasingly recognized to respond to metabolic inputs. In particular, the family of α-ketoglutarate (αKG)-dependent dioxygenases, which include several chromatin-modifying enzymes, are emerging as key mediators of metabolic control of cell fate. αKG-dependent dioxygenases consume the metabolite αKG (also known as 2-oxoglutarate) as an obligate cosubstrate and are inhibited by succinate, fumarate, and 2-hydroxyglutarate. Here, we review the role of these metabolites in the control of dioxygenase activity and cell fate programs. We discuss the biochemical and transcriptional mechanisms enabling these metabolites to control cell fate and review evidence that nutrient availability shapes tissue-specific fate programs via αKG-dependent dioxygenases.

细胞命运决定需要忠实地执行基因表达程序，这些程序越来越被认为对代谢输入做出反应。特别是，α-酮戊二酸 (αKG) 依赖性双加氧酶家族，包括几种染色质修饰酶，正在成为细胞命运代谢控制的关键介质。αKG 依赖性双加氧酶消耗代谢物 αKG（也称为 2-酮戊二酸）作为专性共底物，并被琥珀酸、富马酸和 2-羟基戊二酸抑制。在这里，我们回顾了这些代谢物在控制双加氧酶活性和细胞命运程序中的作用。我们讨论了使这些代谢物能够控制细胞命运的生化和转录机制，并回顾了营养可用性通过 αKG 依赖性双加氧酶塑造组织特异性命运程序的证据。