title: Epigenetic control of rDNA loci in response to intracellular energy status.
abstract: 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.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Murayama
authors.forename: Kazuji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Akiko
authors.initials: A
authors.lastname: Fujimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Minami
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yasuzawa-Tanaka
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Shohei
authors.initials: S
authors.lastname: Oie
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Daitoku
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D016923:Cell Death; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics*; D004734:Energy Metabolism; D020868:Gene Silencing; D005947:Glucose / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D009243:NAD; C407843:SUV39H1 protein, human; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; C529371:RRP8 protein, human; D011495:Histone-Lysine N-Methyltransferase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D005947:Glucose