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

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 ce...

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Bibliographic Details
Published in:	Nature communications 2016-06, Vol.7 (1), p.11807-11807, Article 11807
Main Authors:	Shostak, Anton, Ruppert, Bianca, Ha, Nati, Bruns, Philipp, Toprak, Umut H, Eils, Roland, Schlesner, Matthias, Diernfellner, Axel, Brunner, Michael
Format:	Article
Language:	eng
Subjects:	Cell Cycle - physiology Cell Line Cell Proliferation - physiology Circadian Clocks - physiology Gene Expression Regulation - physiology Humans Kruppel-Like Transcription Factors - genetics Kruppel-Like Transcription Factors - metabolism Lymphoma - metabolism Osteosarcoma - metabolism Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism
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Summary:	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.
ISSN:	2041-1723 2041-1723