Trithoraxregulates long-term memory inDrosophilathrough epigenetic maintenance of mushroom body metabolic identity and translation capacity

Abstract

AbstractThe role of epigenetics and chromatin in the maintenance of postmitotic neuronal cell identities is not well understood. Here, we show that the histone methyltransferase trithorax (trx) is required in postmitotic memory neurons of theDrosophilamushroom body (MB) to enable their capacity for long-term memory (LTM), but not short-term memory (STM). Using MB-specific RNA-, ChIP-, and ATAC-sequencing, we find that trx maintains expression of several non-canonical MB-enriched transcripts, including the orphan nuclear receptorHr51, and the metabolic enzymelactate dehydrogenase. Through these key targets, trx establishes a metabolic state characterized by high lactate levels in MBγ neurons. This metabolic identity supports a high capacity for protein translation, a process that is essential for LTM, but not STM. These data suggest that trx, a classic regulator of cell type specification during development, has an alternative function in maintaining underappreciated aspects of postmitotic neuron identity, such as metabolic state. Our work supports a body of evidence suggesting that a high capacity for energy metabolism is an essential cell identity characteristic for neurons that mediate LTM.