乙酰辅酶A（acetyl-CoA）是乙酰基的活化形式，参与各种乙酰化反应，也是糖类、脂肪、氨基酸氧化时的重要中间产物。组蛋白的乙酰化作用依赖于中间代谢来提供乙酰辅酶A。
然而，乙酰辅酶A也用于脂肪酸的从头合成，在脂肪酸的从头合成过程中，第一个反应同时也是一个限速步骤，即通过乙酰辅酶A羧化酶的催化作用，乙酰辅酶A羧化形成丙二酰辅酶A。所以组蛋白的乙酰化及脂肪酸合成竞争利用了相同的乙酰辅酶A存储库。
近日，来自圣约翰大学的研究人员Ales Vancura等人发现，乙酰辅酶A羧化酶能够调节整体组蛋白的乙酰化，这表明中间代谢影响了组蛋白乙酰化及转录调控。相关研究成果于5月11日发表在The Journal of Biological Chemistry。
在酿酒酵母，已经发现乙酰辅酶A羧化酶由ACC1基因所编码。在这项研究里，他们发现，ACC1的衰减表达会导致批量的组蛋白的乙酰化作用增强，整体的增加了乙酰化的染色体组蛋白，改变了基因转录的调控。
Ales Vancura表示，该研究结果表明，Acc1p调节了乙酰辅酶A对组蛋白乙酰转移酶的可用性，表明了中间代谢与表观遗传调控机制之间的潜在联系。（生物谷Deepblue编译）
doi: 10.1074/jbc.M112.380519
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Acetyl-CoA carboxylase regulates global histone acetylation
Luciano Galdieri and Ales Vancura.
Histone acetylation depends on intermediary metabolism for supplying acetyl-CoA in the nucleocytosolic compartment. However, since nucleocytosolic acetyl-CoA is also used for de novo synthesis of fatty acids, histone acetylation and synthesis of fatty acids compete for the same acetyl-CoA pool.The first and rate-limiting reaction in de novo synthesis of fatty acids is carboxylation of acetyl-CoA to form malonyl-CoA, catalyzed by acetyl-CoA carboxylase.In yeast Saccharomyces cerevisiae, acetyl-CoA carboxylase is encoded by the ACC1 gene.In this study we show that attenuated expression of ACC1 results in increased acetylation of bulk histones, globally increased acetylation of chromatin histones, and altered transcriptional regulation.Together, our data indicate that Acc1p activity regulates the availability of acetyl-CoA for histone acetyltransferases, thus representing a link between intermediary metabolism and epigenetic mechanisms of transcriptional regulation.
