Wellen Kathryn E, Hatzivassiliou Georgia, Sachdeva Uma M, Bui Thi V, Cross Justin R, Thompson Craig B
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2009 May 22;324(5930):1076-80. doi: 10.1126/science.1164097.
Histone acetylation in single-cell eukaryotes relies on acetyl coenzyme A (acetyl-CoA) synthetase enzymes that use acetate to produce acetyl-CoA. Metazoans, however, use glucose as their main carbon source and have exposure only to low concentrations of extracellular acetate. We have shown that histone acetylation in mammalian cells is dependent on adenosine triphosphate (ATP)-citrate lyase (ACL), the enzyme that converts glucose-derived citrate into acetyl-CoA. We found that ACL is required for increases in histone acetylation in response to growth factor stimulation and during differentiation, and that glucose availability can affect histone acetylation in an ACL-dependent manner. Together, these findings suggest that ACL activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression.
单细胞真核生物中的组蛋白乙酰化依赖于利用乙酸盐产生乙酰辅酶A的乙酰辅酶A合成酶。然而，后生动物以葡萄糖作为主要碳源，仅暴露于低浓度的细胞外乙酸盐。我们已经表明，哺乳动物细胞中的组蛋白乙酰化依赖于三磷酸腺苷（ATP）-柠檬酸裂解酶（ACL），该酶将葡萄糖衍生的柠檬酸转化为乙酰辅酶A。我们发现，ACL是响应生长因子刺激和分化过程中组蛋白乙酰化增加所必需的，并且葡萄糖的可利用性可以以ACL依赖的方式影响组蛋白乙酰化。总之，这些发现表明，ACL活性是将生长因子诱导的营养物质代谢增加与组蛋白乙酰化和基因表达的调节联系起来所必需的。
