c-Myc induced changes in higher order rDNA structure accompany growth factor stimulation of quiescent cells

Abstract

Human c-Myc is believed to be a high level coordinator of protein synthesis capacity and cell growth rate, capable of activating transcription by all three nuclear RNA Polymerases. Direct activation of rDNA transcription by c-Myc is functionally conserved in rat cells, despite high divergence in non-coding rDNA sequences, suggesting that this coordinating role is likely to be a general within mammals. Upon re-feeding of starved cells, c-Myc activity enhances the efficiency of RNA Polymerase I and SL1/TIF-1B recruitment to the rDNA and rapidly induces higher order gene loop structures in rDNA chromatin that juxtapose upstream and downstream rDNA sequences. Furthermore c-Myc induced gene-loop formation in rDNA genes occurs independently of rDNA transcription, implying that it may be an early step in the re-programming of quiescent cells as they enter the growth cycle.