The epigenome is sensitive to the availability of metabolites that serve as substrates of chromatin-modifying enzymes. Links between acetyl-CoA metabolism, histone acetylation, and gene regulation have been documented, although how specificity in gene regulation is achieved by a metabolite has been challenging to answer. Recent studies suggest that acetyl-CoA metabolism is tightly regulated both spatially and temporally to elicit responses to nutrient availability and signaling cues. Here we discuss evidence that acetyl-CoA production is differentially regulated in the nucleus and cytosol of mammalian cells. Recent findings indicate that acetyl-CoA availability for site-specific histone acetylation is influenced through post-translational modification of acetyl-CoA-producing enzymes, as well as through dynamic regulation of the nuclear localization and chromatin recruitment of these enzymes.

表观基因组对用作染色质修饰酶底物的代谢物的可用性很敏感。乙酰辅酶A代谢，组蛋白乙酰化和基因调控之间的联系已有文献记载，尽管如何通过代谢物实现基因调控的特异性一直是个难题。最近的研究表明，乙酰辅酶A的代谢在空间和时间上都受到严格调节，以引起对养分有效性和信号提示的响应。在这里，我们讨论的证据表明，乙酰辅酶A的生产在哺乳动物细胞的细胞核和胞质溶胶中受到差异调节。最近的发现表明，乙酰辅酶A对位点特异性组蛋白乙酰化的可用性受乙酰辅酶A产生酶的翻译后修饰影响，