Letter abstract
Nature Cell Biology 7, 311 - 318 (2005)
Published online: 20 February 2005 | doi:10.1038/ncb1224
There is an Addendum (May 2005) associated with this Letter.
c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I
Carla Grandori1,3, Natividad Gomez-Roman2, Zoe A. Felton-Edkins2, Celine Ngouenet3, Denise A. Galloway1, Robert N. Eisenman3 & Robert J. White2
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.
- Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
- Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.
- Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Correspondence to: Carla Grandori1,3 e-mail: cgrandor@fhcrc.org
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