The transcriptional modulator SnoN controls a diverse set of biological 
processes, including cell proliferation and differentiation. The mechanisms by 
which SnoN regulates these processes remain incompletely understood. Recent 
studies have shown that SnoN exerts positive or negative regulatory effects on 
transcription. Because post-translational modification of proteins by small 
ubiquitin-like modifier (SUMO) represents an important mechanism in the control 
of the activity of transcriptional regulators, we asked if this modification 
regulates SnoN function. Here, we show that SnoN is sumoylated. Our data 
demonstrate that the SUMO-conjugating E2 enzyme Ubc9 is critical for SnoN 
sumoylation and that the SUMO E3 ligase PIAS1 selectively interacts with and 
enhances the sumoylation of SnoN. We identify lysine residues 50 and 383 as the 
SUMO acceptor sites in SnoN. Analyses of SUMO "loss-of-function" and 
"gain-of-function" SnoN mutants in transcriptional reporter assays reveal that 
sumoylation of SnoN contributes to the ability of SnoN to repress gene 
expression in a promoter-specific manner. Although this modification has little 
effect on SnoN repression of the plasminogen activator inhibitor-1 promoter and 
only modestly potentiates SnoN repression of the p21 promoter, SnoN sumoylation 
robustly augments the ability of SnoN to suppress transcription of the 
myogenesis master regulatory gene myogenin. In addition, we show that the SnoN 
SUMO E3 ligase, PIAS1, at its endogenous levels, suppresses myogenin 
transcription. Collectively, our findings suggest that SnoN is directly 
regulated by sumoylation leading to the enhancement of the ability of SnoN to 
repress transcription in a promoter-specific manner. Our study also points to a 
physiological role for SnoN sumoylation in the control of myogenin expression in 
differentiating muscle cells.