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c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells

Oncogene volume 28, pages 1833–1842 (2009)Cite this article

Abstract

c-Myc is an oncogenic transcription factor capable of activating transcription by all three nuclear RNA polymerases, thus acting as a high-level coordinator of protein synthesis capacity and cell growth rate. c-Myc recruits RNA polymerase I-related transcription factors to the rDNA when quiescent cells are stimulated to re-enter the cell cycle. Using a model system of cell lines with variable c-Myc status, we show that on stimulation c-Myc rapidly induces gene loop structures in rDNA chromatin that juxtapose upstream and downstream rDNA sequences. c-Myc activation is both necessary and sufficient for this change in rDNA chromatin conformation. c-Myc activation induces association of TTF-1 with the rDNA, and c-Myc is physically associated with induced rDNA gene loops. The origins of two or more rDNA gene loops are closely juxtaposed, suggesting the possibility that c-Myc induces nucleolar chromatin hubs. Induction of rDNA gene loops may be an early step in the reprogramming of quiescent cells as they re-enter the growth cycle.

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Acknowledgements

We thank Lars-Gunnar Larsson for the provision of rat fibroblasts HO15.15, TGR1 and Rat1MycER and Professor Dirk Eick for the generous gift of Smoxi4 cells. This work was supported by a Taiwan Fellowship from the Taiwan Root Medical Peace Corps, the Swedish Cancer Society and the research foundations of the Karolinska Institute.

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  1. Södertörns Högskola and Department of Biosciences and Nutrition, School of Life Sciences, Karolinska Institutet, Huddinge, Sweden

    C-N Shiue, R G Berkson & A P H Wright

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  1. C-N Shiue
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Correspondence to A P H Wright.

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Shiue, CN., Berkson, R. & Wright, A. c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells. Oncogene 28, 1833–1842 (2009). https://doi.org/10.1038/onc.2009.21

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