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The circadian clock and the cell cycle are major cellular systems that organize global physiology in temporal fashion. It seems conceivable that the potentially conflicting programs are coordinated. We show here that overexpression of  MYC  in U2OS cells attenuates the clock and conversely promotes cell proliferation while downregulation of  MYC  strengthens the clock and reduces proliferation. Inhibition of the circadian clock is crucially dependent on the formation of repressive complexes of MYC with MIZ1 and subsequent downregulation of the core clock genes  BMAL1  ( ARNTL ),  CLOCK  and  NPAS2 . We show furthermore that  BMAL1  expression levels correlate inversely with  MYC  levels in 102 human lymphomas. Our data suggest that MYC acts as a master coordinator that inversely modulates the impact of cell cycle and circadian clock on gene expression.

MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation