The Drosophila nuclear receptors EcR and ERR jointly regulate the expression of genes involved in carbohydrate metabolism

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The rate of carbohydrate metabolism is tightly coordinated with developmental transitions in Drosophila, and fluctuates depending on the requirements of a particular developmental stage. These successive metabolic switches result from changes in the expression levels of genes encoding glycolytic, tricarboxylic acid cycle (TCA), and oxidative phosphorylation enzymes. In this report, we describe a repressive action of ecdysone signaling on the expression of glycolytic genes and enzymes of glycogen metabolism in Drosophila development. The basis of this effect is an interaction between the ecdysone receptor (EcR) and the estrogen-related receptor (ERR), a specific regulator of the Drosophila glycolysis. We found an overlapping DNA-binding pattern for the EcR and ERR in the Drosophila S2 cells. EcR was detected at a subset of the ERR target genes responsible for carbohydrate metabolism. The 20-hydroxyecdysone treatment of both the Drosophila larvae and the S2 cells decreased transcriptional levels of ERR targets. We propose a joint action mode for both the EcR and ERR, for at least a subset of the glycolytic genes. We find that both receptors bind to the same regulatory regions and may form or be part of a joint transcriptional regulatory complex in the Drosophila S2 cells.