乙酰輔酶A（acetyl-CoA）是乙酰基的活化形式,，參與各種乙?；磻?yīng)，也是糖類,、脂肪,、氨基酸氧化時的重要中間產(chǎn)物。組蛋白的乙?；饔靡蕾囉谥虚g代謝來提供乙酰輔酶A,。
然而，乙酰輔酶A也用于脂肪酸的從頭合成,，在脂肪酸的從頭合成過程中,，第一個反應(yīng)同時也是一個限速步驟，即通過乙酰輔酶A羧化酶的催化作用,，乙酰輔酶A羧化形成丙二酰輔酶A,。所以組蛋白的乙酰化及脂肪酸合成競爭利用了相同的乙酰輔酶A存儲庫。
近日,，來自圣約翰大學(xué)的研究人員Ales Vancura等人發(fā)現(xiàn),，乙酰輔酶A羧化酶能夠調(diào)節(jié)整體組蛋白的乙酰化,，這表明中間代謝影響了組蛋白乙?；稗D(zhuǎn)錄調(diào)控。相關(guān)研究成果于5月11日發(fā)表在The Journal of Biological Chemistry,。
在釀酒酵母，已經(jīng)發(fā)現(xiàn)乙酰輔酶A羧化酶由ACC1基因所編碼,。在這項研究里,，他們發(fā)現(xiàn)，ACC1的衰減表達會導(dǎo)致批量的組蛋白的乙?；饔迷鰪?，整體的增加了乙酰化的染色體組蛋白,，改變了基因轉(zhuǎn)錄的調(diào)控,。
Ales Vancura表示，該研究結(jié)果表明,，Acc1p調(diào)節(jié)了乙酰輔酶A對組蛋白乙酰轉(zhuǎn)移酶的可用性,，表明了中間代謝與表觀遺傳調(diào)控機制之間的潛在聯(lián)系。（生物谷Deepblue編譯）
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.
