The Drosophila protein Sex Comb on Midleg (Scm) is a member of the Polycomb 
group (PcG), a set of transcriptional repressors that maintain silencing of 
homeotic genes during development. Recent findings have identified PcG proteins 
both as targets for modification by the small ubiquitin-like modifier (SUMO) 
protein and as catalytic components of the SUMO conjugation pathway. We have 
found that the SUMO-conjugating enzyme Ubc9 binds to Scm and that this 
interaction, which requires the Scm C-terminal sterile α motif (SAM) domain, is 
crucial for the efficient sumoylation of Scm. Scm is associated with the major 
Polycomb response element (PRE) of the homeotic gene Ultrabithorax (Ubx), and 
efficient PRE recruitment requires an intact Scm SAM domain. Global reduction of 
sumoylation augments binding of Scm to the PRE. This is likely to be a direct 
effect of Scm sumoylation because mutations in the SUMO acceptor sites in Scm 
enhance its recruitment to the PRE, whereas translational fusion of SUMO to the 
Scm N terminus interferes with this recruitment. In the metathorax, Ubx 
expression promotes haltere formation and suppresses wing development. When SUMO 
levels are reduced, we observe decreased expression of Ubx and partial 
haltere-to-wing transformation phenotypes. These observations suggest that SUMO 
negatively regulates Scm function by impeding its recruitment to the Ubx major 
PRE.