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

Carla Grandori, Natividad Gomez-Roman, Zoe A. Felton-Edkins, Celine Ngouenet, Denise A. Galloway, Robert N. Eisenman, Robert J. White

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440 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalNature Cell Biology
Volume7
Issue number3
DOIs
Publication statusPublished - 20 Feb 2005

Keywords

  • transcription of rRNA genes
  • RNA polymerase I

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