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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 7, Pp 112739- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112739
Popis: 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.
Databáze: Directory of Open Access Journals