Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange
Summary: 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723007507 |
| _version_ | 1797787191269654528 |
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| author | Linda van den Berg Krista Kokki Sylvia J. Wowro Konstantin M. Petricek Onur Deniz Catrin A. Stegmann Marius Robciuc Mari Teesalu Richard G. Melvin Anni I. Nieminen Michael Schupp Ville Hietakangas |
| author_facet | Linda van den Berg Krista Kokki Sylvia J. Wowro Konstantin M. Petricek Onur Deniz Catrin A. Stegmann Marius Robciuc Mari Teesalu Richard G. Melvin Anni I. Nieminen Michael Schupp Ville Hietakangas |
| author_sort | Linda van den Berg |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-13T01:19:26Z |
| format | Article |
| id | doaj.art-65971c572d3b492db9e0387223bacef0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T01:19:26Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-65971c572d3b492db9e0387223bacef02023-07-05T05:15:54ZengElsevierCell Reports2211-12472023-07-01427112739Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orangeLinda van den Berg0Krista Kokki1Sylvia J. Wowro2Konstantin M. Petricek3Onur Deniz4Catrin A. Stegmann5Marius Robciuc6Mari Teesalu7Richard G. Melvin8Anni I. Nieminen9Michael Schupp10Ville Hietakangas11Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandFaculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandCharité – 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, GermanyCharité – 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, GermanyFaculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandCharité – 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, GermanyFaculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandFaculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandSchool of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3083, AustraliaFaculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, FinlandCharité – 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, GermanyFaculty 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723007507CP: Molecular biology |
| spellingShingle | Linda van den Berg Krista Kokki Sylvia J. Wowro Konstantin M. Petricek Onur Deniz Catrin A. Stegmann Marius Robciuc Mari Teesalu Richard G. Melvin Anni I. Nieminen Michael Schupp Ville Hietakangas Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange Cell Reports CP: Molecular biology |
| title | Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange |
| title_full | Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange |
| title_fullStr | Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange |
| title_full_unstemmed | Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange |
| title_short | Sugar-responsive inhibition of Myc-dependent ribosome biogenesis by Clockwork orange |
| title_sort | sugar responsive inhibition of myc dependent ribosome biogenesis by clockwork orange |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723007507 |
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