Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains
Dalton, Justin E. Fear, Justin M. Knott, Simon Baker, Bruce S. McIntyre, Lauren M. Arbeitman, Michelle N.
Bio-Med Central (BMC Genomics)
Background: Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate.
fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific
isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate
Results: By over-expressing individual FruM isoforms in fru-expressing neurons in either males or females and
assaying the global transcriptional response by RNA-sequencing, we show that three FruM isoforms have different
regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of
FruM isoforms, including many annotated with neuronal functions. By determining the binding sites of individual
FruM isoforms using SELEX we demonstrate that the distinct zinc finger domain of each FruM isoforms confers
different DNA binding specificities. A genome-wide search for these binding site sequences finds that the gene sets
identified as induced by over-expression of FruM isoforms in males are enriched for genes that contain the binding
sites. An analysis of the chromosomal distribution of genes downstream of FruM shows that those that are induced
and repressed in males are highly enriched and depleted on the X chromosome, respectively.
Conclusions: This study elucidates the different regulatory and DNA binding activities of three FruM isoforms on a
genome-wide scale and identifies genes regulated by these isoforms. These results add to our understanding of sex
chromosome biology and further support the hypothesis that in some cell-types genes with male-biased
expression are enriched on the X chromosome.
Keywords: Fruitless, Sex hierarchy, Drosophila, Behavior, Genomics, RNA-seq
Dalton et al. BMC Genomics 2013, 14:659
http://www.biomedcentral.com/1471-2164/14/659; Pages 1-15
Cite this article as: Dalton et al.: Male-specific Fruitless isoforms have
different regulatory roles conferred by distinct zinc finger DNA binding
domains. BMC Genomics 2013 14:659.
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1 2 3 4 4 4 5 6 5 F1_SI F2_SI S3_SI F4_SI Gene A Gene B nomenclature of exonic region alternative multigene alternative constitutive common Additional Figure 4 Additional Figure 4: Illustration of Exonic region design and nomenclature. Exonic regions were classied as either belonging to a single exon, S#_SI, or multiple overlapping exons, F#_SI. Multiple overlapping exons consist of exons that were from dierent genes (alternative multigene), overlapping exons due to alternative start and end positions (alternative), or exonic regions present in all isoforms (common).