Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange.

Autor:	van den Berg L; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Kokki K; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Wowro SJ; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, 10117 Berlin, Germany., Petricek KM; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, 10117 Berlin, Germany., Deniz O; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Stegmann CA; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, 10117 Berlin, Germany., Robciuc M; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Teesalu M; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Melvin RG; School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3083, Australia., Nieminen AI; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland., Schupp M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, 10117 Berlin, Germany., Hietakangas V; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland. Electronic address: ville.hietakangas@helsinki.fi.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jul 25; Vol. 42 (7), pp. 112739. Date of Electronic Publication: 2023 Jul 04.
DOI:	10.1016/j.celrep.2023.112739
Abstrakt:	The ability to feed on a sugar-containing diet depends on a gene regulatory network controlled by the intracellular sugar sensor Mondo/ChREBP-Mlx, which remains insufficiently characterized. Here, we present a genome-wide temporal clustering of sugar-responsive gene expression in Drosophila larvae. We identify gene expression programs responding to sugar feeding, including downregulation of ribosome biogenesis genes, known targets of Myc. Clockwork orange (CWO), a component of the circadian clock, is found to be a mediator of this repressive response and to be necessary for survival on a high-sugar diet. CWO expression is directly activated by Mondo-Mlx, and it counteracts Myc through repression of its gene expression and through binding to overlapping genomic regions. CWO mouse ortholog BHLHE41 has a conserved role in repressing ribosome biogenesis genes in primary hepatocytes. Collectively, our data uncover a cross-talk between conserved gene regulatory circuits balancing the activities of anabolic pathways to maintain homeostasis during sugar feeding. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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