Integrated CUT&Tag and mRNA-seq profiling of histone H2AK5 mutants reveals epigenetic and transcriptional changes associated with male-directed courtship in Drosophila males

Courtship target selection in males must be stable enough to preserve a sex-specific behavioral program, yet flexible enough to be tuned by adult physiological state and experience. This project aims to explain why histone mutant Drosophila males display male-directed courtship. We focus on regulation linked to histone H2A lysine 5 (H2AK5), including H2AK5 point mutants (e.g., H2AK5A/H2AK5R) and related genetic perturbations (for example, manipulating the acetyltransferase P300 and/or downstream signaling nodes).To define molecular changes underlying this behavioral bias, we performed CUT&Tag on adult head/brain tissue to profile genome-wide occupancy of key chromatin features and/or associated factors, and mRNA-seq to quantify transcriptome responses. Integrating these epigenomic and transcriptomic datasets enables identification of core downstream targets and pathways associated with altered courtship-choice thresholds, providing a resource to study how epigenetic state interfaces with neuronal signaling and behavior.