Abstract
Nutrient-dependent gene regulation critically contributes to homeostatic control of animal physiology in changing nutrient landscape. In Drosophila, dietary sugars activate transcription factors (TFs), such as Mondo-Mlx, Sugarbabe and Cabut, which control metabolic gene expression to mediate physiological adaptation to high sugar diet. TFs that correspondingly control sugar responsive metabolic genes under conditions of low dietary sugar remain, however, poorly understood. Here we identify a role for Drosophila GATA TF Grain in metabolic gene regulation under both low and high sugar conditions. De novo motif prediction uncovered a significant over-representation of GATA-like motifs on the promoters of sugar-activated genes in Drosophila larvae, which are regulated by Grain, the fly ortholog of GATA1/2/3 subfamily. grain expression is activated by sugar in Mondo-Mlx-dependent manner and it contributes to sugar-responsive gene expression in the fat body. On the other hand, grain displays strong constitutive expression in the anterior midgut, where it drives lipogenic gene expression also under low sugar conditions. Consistently with these differential tissue-specific roles, Grain deficient larvae display delayed development on high sugar diet, while showing deregulated central carbon and lipid metabolism primarily on low sugar diet. Collectively, our study provides evidence for the role of a metazoan GATA transcription factor in nutrient-responsive metabolic gene regulation in vivo.
Highlights
Animal physiology is constantly readjusted in changing nutrient landscape
Through an unbiased in silico search of candidate transcription factors involved in sugardependent gene regulation, we have discovered that Drosophila GATA transcription factor Grain contributes to the regulation of a specific subset of sugar responsive genes
We provide evidence for a role for GATA transcription factor Grain in metabolic gene regulation in vivo (Fig 11)
Summary
Animal physiology is constantly readjusted in changing nutrient landscape. The ability to control systemic metabolism with respect to nutrient content is due to so-called nutrient sensing pathways. They are composed of inter- and intracellular signaling pathways and gene regulatory networks that control the activity of metabolic genes and gene products [1,2]. A key regulator of dietary sugar responsive gene expression is the heterodimeric basic helix-loop-helix.
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