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Metabolic gene regulation by Drosophila GATA transcription factor Grain

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. 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE166681 | GEO | 2021/10/06

REPOSITORIES: GEO

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Project description:Analysis of wildtype C. elegans (N2) and pcca-1(ok2282) and metr-1(ok521) mutants fed Comamonas DA1877 Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network comprised of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several TFs that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network comprised of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several TFs that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. 3 biological replicates for each condition, wild type is reference sample

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Metabolic gene regulation by Drosophila GATA transcription factor Grain

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