The Drosophila SWI/SNF complex sub-unit Bap60 is required for training-induced gene transcription during long-term...

Long-term memory (LTM) formation requires activated gene expression in response to neuronal activity. Chromatin remodeling is thought to play a role in this transcriptional response, but the mechanisms remain unclear. In Drosophila melanogaster, a transcriptional trace of courtship LTM training can be observed in the mushroom body (MB) during the memory consolidation phase after the end of training. We investigated the role of Bap60, a core subunit of the SWI/SNF chromatin remodeling complex, in the transcriptional trace of memory consolidation. Knockdown of Bap60 in the adult MB impaired LTM. Transcriptome analysis of MB neurons following training revealed disruption of training-induced transcription in Bap60 knockdown MBs. MB-specific CUT&RUN for Brm was used to map SWI/SNF binding sites and identify 142 Bap60-regulated Brm-bound genes. Bap60 was not required for training-induced activation of immediate early genes (IEGs), Hr38 and sr, which encode critical LTM transcription factors. This suggests that Bap60 regulates LTM gene induction downstream of, or in cooperation with IEGs. In support of this, we identified Sr binding sites at 43/142 of Bap60-regulated Brm-bound genes. Among the Bap60 and Sr target genes, we identified prospero, encoding a transcription factor with known roles in MB development. Knockdown of Prospero in the adult MB impaired LTM and Prospero DNA binding sites were identified at 46/142 of Bap60-regulated Brm-bound genes. This suggests that Prospero is an important transcription factor for LTM within the Bap60-regulated gene network. This work implicates Bap60 as a central player in activation of the transcriptional trace of memory consolidation.