Central regulation of lipid metabolism and starvation response by a histone acetyl-transferase. Nina Moderau, Ingo Zinke, Michael J. Pankratz. Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, 53115 Bonn, Germany.
Histone acetylation plays a key role in chromatin remodeling and regulates many processes, including development and cell proliferation. Through this epigenetic modification chromatin is decondensed and allows the transcriptional machinery to access the genes. We identified Enoki mushoom (Enok) a MYST Histone Acetyl-Transferase (HAT), as an epigenetic metabolic regulator. Enok autonomously controls neuronal stem cell division as well as growth, feeding behavior and nutritional homeostasis, especially lipid catabolism. Immunofluorescence microscopy reveals that Enok is expressed during second and third larval stage in oenocytes in periphery, a special type of glial cells and neuronal stem cells in the CNS. These tissues play important role in nutrient storage, metabolism and growth control. Animals with tissue-specific overexpression of Enok protein showed no change in lipid content and lipid depletion under starvation conditions. Transcriptional analysis by microarrays and qPCR suggests that Enok controls the activity of genes involved in lipolysis and -oxidation. Altogether, we demonstrate that Enok controls lipid metabolism in the periphery, as well as in the CNS, and regulates the global starvation response. We provide a model for the transcriptional regulation of lipolysis and -oxidation genes by Enok on an epigenetic level.