TaDa! Discovering a Novel Role of Sex Lethal in Sexual Development of the Fruit Fly

Assessing time-specific transcriptomes or global genomic interactions of transcription factors in particular tissues has been a great challenge to biologists for decades. TaDa, Targeted DamID, offers a non-intrusive, in vivo method to identify DNA-binding targets in a spatio-& temporal-specific manner which is relatively cheap and requires little starting material. We utilised this technique in Drosophila melanogaster to investigate the associations of the well characterised sexual determination gene Sex Lethal across the genome at different stages of development in the brain of both sexes. We identify that Sxl associates with ~30% of genes across the genome in both male and female larvae while no significant binding is observed in adults. Furthermore Sxl was found to be in proximity to a high proportion of sex-biased genes in neurons, binding more frequently to those upregulated in the ovaries and down-regulated in the testis, and associating with transcribed genes more often than those that aren’t. Together these results suggest that Sxl has a larval-specific DNA-associated function in sexual determination in addition to its known role in mRNA-splicing. This study demonstrates the versatility and impact TaDa offers as a technique to geneticists and developmental biologists in understanding the role of transcription factors and transcriptional changes in defining tissue development and function.