Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene transcription

Mol Cell. 2001 Sep;8(3):719-25. doi: 10.1016/s1097-2765(01)00317-3.


Epigenetic control mechanisms silence about half of ribosomal RNA genes (rDNA) in metabolically active cells. In the mouse, 40% of rDNA repeats are methylated and can be activated by 5-azacytidine treatment. In exploring the effect of methylation on rDNA transcription, we found that methylation of a single CpG dinucleotide within the upstream control element of the rDNA promoter (at -133) abrogates rDNA transcription both in transfection experiments and in in vitro assays using chromatin templates. Chromatin immunoprecipitation assays demonstrate that methylation of the cytosine at -133 inhibits binding of the transcription factor UBF to nucleosomal rDNA, thereby preventing initiation complex formation. Thus, methylation may be a mechanism to inactivate rDNA genes and propagate transcriptional silencing through cell division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Azacitidine / pharmacology
  • Chromatin / genetics
  • Chromatin / metabolism
  • CpG Islands / genetics
  • DNA Footprinting
  • DNA Methylation
  • DNA, Ribosomal / genetics
  • DNA, Ribosomal / metabolism*
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Silencing*
  • Genes, Reporter / genetics
  • Genes, rRNA*
  • Mice
  • Nuclear Proteins / metabolism
  • Precipitin Tests
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics*


  • Chromatin
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Azacitidine