Epigenetic control of rDNA loci in response to intracellular energy status

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.

MeSH terms

  • Cell Death
  • Cell Line
  • Cell Nucleolus / metabolism
  • DNA, Ribosomal / genetics*
  • Energy Metabolism*
  • Gene Silencing*
  • Glucose / metabolism
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Humans
  • Methyltransferases / chemistry
  • Methyltransferases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • NAD / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Protein Methyltransferases
  • Protein Structure, Tertiary
  • RNA-Binding Proteins
  • Repressor Proteins / metabolism
  • Sirtuin 1
  • Sirtuins / metabolism
  • Transcription, Genetic*


  • DNA, Ribosomal
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • NAD
  • SUV39H1 protein, human
  • Histone Methyltransferases
  • Methyltransferases
  • Protein Methyltransferases
  • nucleomethylin protein, human
  • Histone-Lysine N-Methyltransferase
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Glucose

Associated data

  • GENBANK/O43159
  • PDB/2ZFU