Over-expression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype

Background: DNA replication-related element binding factor (DREF) has been suggested to be involved in regulation of DNA replication- and proliferatio n-related genes in Drosophila. While the effects on the mutation in the DNA replication-related element (DRE) in cultured cells have been studied exte nsively, the consequences of elevating wild-type DREF activity in developin g tissues have hitherto remained unclear. Results: We over-expressed DREF in the wing imaginal disc using a GAL4-UAS targeted expression system in Drosophila. Over-expression of DREF induced a notching wing phenotype, which was associated with ectopic apoptosis. A ha lf reduction of the reaper, head involution defective and grim gene dose su ppressed this DREF-induced notching wing phenotype. Furthermore, this was a lso the case with co-expression of baculovirus P35, a caspase inhibitor. In addition, overexpression of the 32 kDa boundary element-associated factor (BEAF-32), thought to compete against DREF for common binding sites in geno mic regions, rescued the DREF-induced notching wing phenotype, while a half reduction of the genomic region, including the BEAF-32 gene, exerted enhan cing effects. To our knowledge, this is the first evidence for a genetic in teraction between DREF and BEAF-32. Conclusion: The DREF-induced notching wing phenotype is caused by induction of apoptosis in the Drosophila wing imaginal disc.