The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing. (27th April 2015)

• Record Type: Journal Article
• Authors: Bartok, Osnat; Teesalu, Mari; Ashwall‐Fluss, Reut; Pandey, Varun; Hanan, Mor; Rovenko, Bohdana M; Poukkula, Minna; Havula, Essi; Moussaieff, Arieh; Vodala, Sadanand; Nahmias, Yaakov; Kadener, Sebastian; Hietakangas, Ville
• Is Part Of: EMBO journal. Volume 34:Number 11(2015)
• Page Start: 1538
• Page End: 1553
• Publication Date: 2015-04-27
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201591385
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201591385-abs-0001"> <title>Abstract</title> <p>Nutrient sensing pathways adjust metabolism and physiological functions in response to food intake. For example, sugar feeding promotes lipogenesis by activating glycolytic and lipogenic genes through the Mondo/ChREBP‐Mlx transcription factor complex. Concomitantly, other metabolic routes are inhibited, but the mechanisms of transcriptional repression upon sugar sensing have remained elusive. Here, we characterize <italic>cabut</italic> (<italic>cbt</italic>), a transcription factor responsible for the repressive branch of the sugar sensing transcriptional network in <italic>Drosophila</italic>. We demonstrate that <italic>cbt</italic> is rapidly induced upon sugar feeding through direct regulation by Mondo‐Mlx. We found that CBT represses several metabolic targets in response to sugar feeding, including both isoforms of <italic>phosphoenolpyruvate carboxykinase</italic> (<italic>pepck</italic>). Deregulation of <italic>pepck1</italic> (CG17725) in <italic>mlx</italic> mutants underlies imbalance of glycerol and glucose metabolism as well as developmental lethality. Furthermore, we demonstrate that <italic>cbt</italic> provides a regulatory link between nutrient sensing and the circadian clock. Specifically, we show that a subset of genes regulated by the circadian clock are also targets of CBT. Moreover, perturbation of CBT levels leads to deregulation of the circadian transcriptome and circadian behavioral patterns.</p> </abstract>