Murayama Akiko, Ohmori Kazuji, Fujimura Akiko, Minami Hiroshi, Yasuzawa-Tanaka Kayoko, Kuroda Takao, Oie Shohei, Daitoku Hiroaki, Okuwaki Mitsuru, Nagata Kyosuke, Fukamizu Akiyoshi, Kimura Keiji, Shimizu Toshiyuki, Yanagisawa Junn
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
Cell. 2008 May 16;133(4):627-39. doi: 10.1016/j.cell.2008.03.030.
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.
细胞内的能量平衡对细胞存活至关重要。在真核细胞中，最消耗能量的过程是核糖体生物合成，它会适应细胞内能量状态的变化。然而，将能量状态与核糖体生物合成联系起来的机制在很大程度上尚不清楚。在此，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包含Nucleomethylin，它与SIRT1和SUV39H1形成复合物，结合rDNA位点中二甲基化赖氨酸9处的组蛋白H3。SIRT1和SUV39H1都是能量依赖性转录抑制所必需的，这表明能量状态降低引起的NAD(+)/NADH比值变化可激活SIRT1，导致组蛋白H3去乙酰化以及SUV39H1使赖氨酸9处发生二甲基化，从而在rDNA位点建立沉默染色质。此外，eNoSC通过限制rRNA转录促进能量平衡的恢复，从而保护细胞免受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见解。
