Takahashi Hidekazu, McCaffery J Michael, Irizarry Rafael A, Boeke Jef D
High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Cell. 2006 Jul 21;23(2):207-17. doi: 10.1016/j.molcel.2006.05.040.
Metabolic enzymes rarely regulate informational processes like gene expression. Yeast acetyl-CoA synthetases (Acs1p and 2p) are exceptional, as they are important not only for carbon metabolism but also are shown here to supply the acetyl-CoA for histone acetylation by histone acetyltransferases (HATs). acs2-Ts mutants exhibit global histone deacetylation, transcriptional defects, and synthetic growth defects with HAT mutants at high temperatures. In glycerol with ethanol, Acs1p is an alternate acetyl-CoA source for HATs. Rapid deacetylation after Acs2p inactivation suggests nuclear acetyl-CoA synthesis is rate limiting for histone acetylation. Different histone lysines exhibit distinct deacetylation rates, with N-terminal tail lysines deacetylated rapidly and H3 lysine 56 slowly. Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. Thus, acetyl-CoA metabolism is directly linked to chromatin regulation and may affect diverse cellular processes in which acetylation and metabolism intersect, such as disease states and aging.
代谢酶很少调节像基因表达这样的信息过程。酵母乙酰辅酶A合成酶（Acs1p和2p）是个例外，因为它们不仅对碳代谢很重要，而且在此处还显示可通过组蛋白乙酰转移酶（HATs）为组蛋白乙酰化提供乙酰辅酶A。acs2 - Ts突变体在高温下表现出整体组蛋白去乙酰化、转录缺陷以及与HAT突变体的合成生长缺陷。在甘油与乙醇存在的情况下，Acs1p是HATs的另一种乙酰辅酶A来源。Acs2p失活后的快速去乙酰化表明核内乙酰辅酶A合成是组蛋白乙酰化的限速步骤。不同的组蛋白赖氨酸表现出不同的去乙酰化速率，N端尾巴赖氨酸快速去乙酰化，而H3赖氨酸56则缓慢去乙酰化。酵母线粒体和核质乙酰辅酶A池在生化上是隔离的。因此，乙酰辅酶A代谢与染色质调节直接相关，并且可能影响乙酰化和代谢相互交叉的各种细胞过程，如疾病状态和衰老。
