Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, The University of Michigan, Ann Arbor, United States
Anoumid Vaziri
Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, The University of Michigan, Ann Arbor, United States; The Molecular, Cellular and Developmental Biology Graduate Program, The University of Michigan, Ann Arbor, United States
Daniel Wilinski
Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, The University of Michigan, Ann Arbor, United States
Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, The University of Michigan, Ann Arbor, United States
Department of Biological Chemistry, The University of Michigan Medical School, Ann Arbor, United States; Department of Computational Medicine and Bioinformatics, The University of Michigan Medical School, Ann Arbor, United States
Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, The University of Michigan, Ann Arbor, United States; The Molecular, Cellular and Developmental Biology Graduate Program, The University of Michigan, Ann Arbor, United States; The Michigan Neuroscience Institute, Ann Arbor, United States
Diet profoundly influences brain physiology, but how metabolic information is transmuted into neural activity and behavior changes remains elusive. Here, we show that the metabolic enzyme O-GlcNAc Transferase (OGT) moonlights on the chromatin of the D. melanogaster gustatory neurons to instruct changes in chromatin accessibility and transcription that underlie sensory adaptations to a high-sugar diet. OGT works synergistically with the Mitogen Activated Kinase/Extracellular signal Regulated Kinase (MAPK/ERK) rolled and its effector stripe (also known as EGR2 or Krox20) to integrate activity information. OGT also cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to decrease chromatin accessibility and repress transcription in the high-sugar diet. This integration of nutritional and activity information changes the taste neurons’ responses to sugar and the flies’ ability to sense sweetness. Our findings reveal how nutrigenomic signaling generates neural activity and behavior in response to dietary changes in the sensory neurons.
