1. Metabolic gene regulation by Drosophila GATA transcription factor Grain
- Author
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Essi Havula, Marius R. Robciuc, Bohdana M. Rovenko, Ville Hietakangas, Krista Kokki, Anni I. Nieminen, Nicole Lamichane, Reijo Käkelä, Jack Morikka, Hanna Ruhanen, Molecular and Integrative Biosciences Research Programme, Centre of Excellence in Stem Cell Metabolism, Nutrient sensing laboratory, Institute for Molecular Medicine Finland, Functional Lipidomics Group, and STEMM - Stem Cells and Metabolism Research Program
- Subjects
EXPRESSION ,Transcriptional Activation ,Cancer Research ,DATABASE ,ENERGY-METABOLISM ,QH426-470 ,MASS ,Biology ,GATA Transcription Factors ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,Genetics ,Transcriptional regulation ,Animals ,Drosophila Proteins ,Molecular Biology ,Gene ,Transcription factor ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,2. Zero hunger ,Regulation of gene expression ,0303 health sciences ,fungi ,1184 Genetics, developmental biology, physiology ,Promoter ,GATA1 ,Cell biology ,LIFE ,SEQ ,Gene Expression Regulation ,DISCOVERY ,Larva ,GROWTH ,GATA transcription factor ,Drosophila ,Sugars ,030217 neurology & neurosurgery ,Research Article - 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.
- Published
- 2021