c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells.
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.
Shiue
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CN
Södertörns Högskola and Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Berkson
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Wright
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AP
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004275:DNA, Ribosomal / Q000737:chemistry*; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012318:RNA Polymerase I / Q000737:chemistry; D051381:Rats; D035181:TATA-Box Binding Protein / Q000737:chemistry; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D035181:TATA-Box Binding Protein; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D012318:RNA Polymerase I