Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes.
Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes.
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DOI：
10.1016/j.molcel.2011.05.004
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发表时间：
2011-05-20
期刊：
影响因子：
16
通讯作者：
Tu BP
中科院分区：
文献类型：
--
作者：
Cai L;Sutter BM;Li B;Tu BP
一个细胞进入一轮生长和分裂的决定必须与营养物质的可利用性及其代谢状态密切协调。这些代谢和营养需求，以及它们诱导细胞生长和增殖的机制，仍然知之甚少。在此，我们报道乙酰辅酶A是碳源的下游代谢产物，它是生长和增殖的关键代谢信号。在进入生长阶段时，细胞内乙酰辅酶A水平大幅增加，进而诱导Gcn5p/SAGA在对生长重要的基因上催化组蛋白乙酰化，从而使其能够快速转录并致力于生长。因此，乙酰辅酶A作为一种碳源变阻器发挥作用，通过促进组蛋白在生长基因上的特异性乙酰化来发出细胞生长程序启动的信号。
The decision by a cell to enter a round of growth and division must be intimately coordinated with nutrient availability and its metabolic state. These metabolic and nutritional requirements, and the mechanisms by which they induce cell growth and proliferation, remain poorly understood. Herein, we report that acetyl-CoA is the downstream metabolite of carbon sources that represents a critical metabolic signal for growth and proliferation. Upon entry into growth, intracellular acetyl-CoA levels increase substantially and consequently induce the Gcn5p/SAGA-catalyzed acetylation of histones at genes important for growth, thereby enabling their rapid transcription and commitment to growth. Thus, acetyl-CoA functions as a carbon-source rheostat that signals the initiation of the cellular growth program by promoting the acetylation of histones specifically at growth genes.
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