西亚试剂：Epigenetic Control of rDNA Loci in Response to Intracellula

发布时间：2025-08-27

Control of rDNA Loci in Response to Intracellular Energy Status
Akiko Murayama,1,2,5,6 Kazuji Ohmori,1,6 Akiko Fujimura,1 Hiroshi Minami,4 Kayoko Yasuzawa-Tanaka,1 Takao Kuroda,1 Shohei Oie,1 Hiroaki Daitoku,2 Mitsuru Okuwaki,3 Kyosuke Nagata,3 Akiyoshi Fukamizu,2 Keiji Kimura,1 Toshiyuki Shimizu,4 and Junn Yanagisawa1,

1 Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
2 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
3 Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
4 International Graduate School of Arts and Sciences, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan
5 PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama, Japan

Corresponding author
Junn Yanagisawa
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.

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