Epigenetic control of rDNA loci in response to intracellular energy status
Epigenetic control of rDNA loci in response to intracellular energy status
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DOI：
10.1016/j.cell.2008.03.030
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发表时间：
2008-05-16
期刊：
影响因子：
64.5
通讯作者：
Yanagisawa, Junn
中科院分区：
文献类型：
--
作者：
Murayama, Akiko;Ohmori, Kazuji;Yanagisawa, Junn
细胞内的能量平衡对细胞的存活很重要。在真核细胞中，最消耗能量的过程是核糖体生物合成，它适应细胞内能量状态的变化。然而，连接能量状态和核糖体生物合成的机制在很大程度上是未知的。在这里，我们描述了eNoSC，一种感知能量状态并控制rRNA转录的蛋白质复合物。eNoSC含有Nucleomethylin，其在与SIRT 1和SUV 39 H1的复合物中结合rDNA基因座中的组蛋白H3二甲基化Lys 9。SIRT 1和SUV 39 H1都是能量依赖性转录抑制所必需的，这表明能量状态降低诱导的NAD（+）/NADH比率的变化可以激活SIRT 1，导致组蛋白H3的脱乙酰化和SUV 39 H1在Lys 9的二甲基化，从而在rDNA基因座中建立沉默的染色质。此外，eNoSC通过限制rRNA转录促进能量平衡的恢复，从而保护细胞免于能量剥夺依赖性凋亡。这些发现为细胞能量稳态机制提供了关键的见解。
Intracellular energy balance is important for cell survival. In eukaryotic cells, the most energy-consuming process is ribosome biosynthesis, which adapts to changes in intracellular energy status. However, the mechanism that links energy status and ribosome biosynthesis is largely unknown. Here, we describe eNoSC, a protein complex that senses energy status and controls rRNA transcription. eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. Both SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression, suggesting that a change in the NAD(+)/NADH ratio induced by reduction of energy status could activate SIRT1, leading to deacetylation of histone H3 and dimethylation at Lys9 by SUV39H1, thus establishing silent chromatin in the rDNA locus. Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. These findings provide key insight into the mechanisms of energy homeostasis in cells.