Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends Biochem Sci. 2018 Jan;43(1):61-74. doi: 10.1016/j.tibs.2017.11.004. Epub 2017 Nov 23.
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.
表观基因组对作为染色质修饰酶底物的代谢物的可用性敏感。已经记录了乙酰辅酶 A 代谢、组蛋白乙酰化和基因调控之间的联系，尽管代谢物如何实现基因调控的特异性一直是一个具有挑战性的问题。最近的研究表明，乙酰辅酶 A 代谢在空间和时间上受到严格调控，以对营养物质的可用性和信号线索做出反应。在这里，我们讨论了证据表明乙酰辅酶 A 的产生在哺乳动物细胞的核和细胞质中是不同调节的。最近的发现表明，通过乙酰辅酶 A 产生酶的翻译后修饰，以及通过这些酶的核定位和染色质募集的动态调节，影响了用于特定位置组蛋白乙酰化的乙酰辅酶 A 的可用性。
