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Nat Cell Biol. 2005 Mar;7(3):311-8.

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

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  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. cgrandor@fhcrc.org

Erratum in

  • Nat Cell Biol. 2005 May;7(5):531.

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.

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PMID:
15723054
[PubMed - indexed for MEDLINE]
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