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Oncogene. 2009 Apr 23;28(16):1833-42. doi: 10.1038/onc.2009.21. Epub 2009 Mar 9.

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

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Södertörns Högskola and Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.


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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