c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I

Nat Cell Biol. 2005 Mar;7(3):311-8. doi: 10.1038/ncb1224.


c-Myc coordinates cell growth and division through a transcriptional programme that involves both RNA polymerase (Pol) II- and Pol III-transcribed genes. Here, we demonstrate that human c-Myc also directly enhances Pol I transcription of ribosomal RNA (rRNA) genes. rRNA synthesis and accumulation occurs rapidly following activation of a conditional MYC-ER allele (coding for a Myc-oestrogen-receptor fusion protein), is resistant to inhibition of Pol II transcription and is markedly reduced by c-MYC RNA interference. Furthermore, by using combined immunofluorescence and rRNA-FISH, we have detected endogenous c-Myc in nucleoli at sites of active ribosomal DNA (rDNA) transcription. Our data also show that c-Myc binds to specific consensus elements located in human rDNA and associates with the Pol I-specific factor SL1. The presence of c-Myc at specific sites on rDNA coincides with the recruitment of SL1 to the rDNA promoter and with increased histone acetylation. We propose that stimulation of rRNA synthesis by c-Myc is a key pathway driving cell growth and tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Nucleolus / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • DNA / chemistry
  • DNA Primers / chemistry
  • DNA, Ribosomal / chemistry*
  • DNA, Ribosomal / metabolism
  • Fibroblasts / metabolism
  • G1 Phase
  • HeLa Cells
  • Histones / chemistry
  • Humans
  • Immunoprecipitation
  • In Situ Hybridization, Fluorescence
  • Microscopy, Fluorescence
  • Models, Genetic
  • Neoplasms / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Interference
  • RNA Polymerase I / metabolism*
  • RNA, Ribosomal / metabolism
  • Resting Phase, Cell Cycle
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic*


  • DNA Primers
  • DNA, Ribosomal
  • Histones
  • Proto-Oncogene Proteins c-myc
  • RNA, Ribosomal
  • DNA
  • RNA Polymerase I