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

Nature Cell Biology volume 7, pages 311–318 (2005)Cite this article

An Addendum to this article was published on 01 May 2005

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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Figure 1: rRNA synthesis responds to c-Myc levels.
Figure 2: Analysis of pre-rRNA synthesis following Myc-ER activation.
Figure 3: Endogenous c-Myc localizes in nucleoli during the G0/G1 transition.
Figure 4: c-Myc binds to specific regions of human ribosomal DNA (rDNA).
Figure 5: Changes in Pol I machinery and histone acetylation at ribosomal DNA (rDNA) in response to c-Myc.

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Acknowledgements

We thank L. Comai and J. Flint for generous gifts of antibodies and A. Burdick and K. Robinson for technical assistance; J. Benanti, M. Welcker and B. Moorefield for critical reading of the manuscript; T. Ragoczy, S. Kosak, M. Lorincz and D. Dickerson in the Groudine laboratory for advice on FISH and run-on assays; T. Sawado for the ChIP protocol; and the Fred Hutchinson Image Analysis staff for help with DeltaVision microscopy. We are also grateful to R. Reeder for helpful discussions during the course of this work. Support for this work was from National Institutes of Health grants to C.G. D.A.G. and R.N.E.; and Cancer Research UK grants to R.J.W. R.N.E. is an American Cancer Society Research professor.

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Authors and Affiliations

  1. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109-1024, WA, USA

    Carla Grandori & Denise A. Galloway

  2. Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

    Natividad Gomez-Roman, Zoe A. Felton-Edkins & Robert J. White

  3. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109-1024, WA, USA

    Carla Grandori, Celine Ngouenet & Robert N. Eisenman

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Correspondence to Carla Grandori.

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Grandori, C., Gomez-Roman, N., Felton-Edkins, Z. et al. c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7, 311–318 (2005). https://doi.org/10.1038/ncb1224

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