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Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains

Justin E Dalton1, Justin M Fear234, Simon Knott5, Bruce S Baker6, Lauren M McIntyre34 and Michelle N Arbeitman17*

Author Affiliations

1 Biomedical Sciences Department and Program in Neuroscience, Florida State University, College of Medicine, Tallahassee, FL 32303, USA

2 Genetics and Genomics Graduate Program, University of Florida, Gainesville, FL, USA

3 Genetics Institute, University of Florida, Gainesville, FL, USA

4 Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA

5 Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA

6 Janelia Farm Research Campus, HHMI, 19700 Helix Drive, Ashburn, VA 20147, USA

7 Department of Biomedical Sciences, Florida State University, 1115 West Call Street, Tallahassee, FL 32306, USA

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BMC Genomics 2013, 14:659  doi:10.1186/1471-2164-14-659

Published: 27 September 2013



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 DNA binding.


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.


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.

Fruitless; Sex hierarchy; Drosophila; Behavior; Genomics; RNA-seq