Metabolic gene regulation by Drosophila GATA transcription factor Grain

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. We have used de novo motif prediction to uncover a significant over-representation of GATA-like motifs on the promoters of sugar-responsive genes in Drosophila larvae. GATA TF Grain was found to contribute to the regulation of sugar-responsive genes, and consequently to central carbon and lipid metabolism, primarily on low sugar diet. Grain targets include known sugar responsive TFs, cabut and smad on X (smox). Moreover, Grain promotes the expression of genes involved in de novo lipogenesis. Grain chromatin binding sites significantly converge with those of Sugarbabe. Grain and Sugarbabe both activate lipogenic genes, but display functional predominance on low and high sugar conditions, respectively. Collectively, our data provides evidence for a metazoan GATA transcription factor in nutrient-responsive metabolic regulation in vivo. Overall design: 1st instar larvae were collected 24 hours after egg laying to plates with LSD (low sugar diet, 10% yeast) at a controlled density. Early 2nd instar larvae were transferred at 48 hours after egg laying to plates containing either LSD or HSD (high sugar diet, 10% yeast supplemented with 15% sugar). After 8 hours of diet exposure, 20 larvae per sample were collected and snap-frozen in liquid nitrogen.