Post-translational modification of Vestigial modulates transcriptional response in developing wing cells. Virginia Pimmett¹, Hua Deng², Andrew Simmonds¹. 1) Cell Biology, University of Alberta, Edmonton, Alberta, Canada; 2) Molecular Biology & Genetics, Johns Hopkins University, Baltimore, Maryland, USA.

   The transcriptional co-activator Vestigial (VG) is a key selector in determining cell fate in the developing wing disc. Together with its partner transcription factor Scalloped (SD), VG coordinates activation of the expression of many key wing-specification genes through activation of target enhancers in cells within the wing pouch. It has been shown previously by Takanaka and Courey (Mech. Dev, 122, pp 1030-7, 2005) that VG is SUMOylated and that this might be important for VG function. We have found that specific post-translational modifications of VG through phosphorylation by mitogen-activated protein kinase (MAPK) and conjugation of a small ubiquitin-like modifier (SUMO) to a specific lysine residue are important in determining the ability of VG and SD to activate target enhancers in vitro and in vivo. We have identified the target lysine residue for SUMO conjugation as well as a key residue targeted by p38b MAPK that is important for proper transcriptional activation in wing discs. Mutation of these sites, as well as blocking the modification pathways, alters the ability of a SD/VG complex to activate the Vestigial quadrant (VgQ) enhancer in vitro. Furthermore, we show that blocking these modifications has transcriptional and phenotypic consequences in vivo. Post-translational modification of VG has been experimentally shown to be dependent on a scaffolding function of SD. Together this indicates a possible mechanism for restriction of target gene expression to specific cells within the developing wing primordia.