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Energy metabolism modulates the regulatory impact of gene activators on protein expression

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Gene expression is a regulated process that is driven by ATP consumption. Therefore, regulation must be coupled to constraints imposed by the level of energy metabolism. Here, we explore this relationship both theoretically and experimentally. A mathematical model predicts that activators of gene expression have variable impact depending on metabolic rate. Activators become less essential when metabolism is reduced and more essential when metabolism is enhanced. We find that in the Drosophila eye, expression dynamics of the yan gene are less affected by loss of EGFR-mediated activation when metabolism is reduced, and the opposite effect is seen when metabolism is enhanced. The effects are also seen at the level of pattern regularity in the adult eye, where loss of EGFR-mediated activation is mitigated by lower metabolism. We propose that gene activation is tuned by energy metabolism to allow for faithful expression dynamics in the face of variable metabolic conditions.

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  • 03/15/2023
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