Regulatory transcription factors of the Pax family play fundamental roles in the 
function of multipotent cells during vertebrate development, post-natal 
regeneration, and cancer. Pax7 and its homologue Pax3 are important players in 
neural crest and muscle development. Both genes are coexpressed in various 
tissues and are thought to provide similar, but not identical, functions. The 
mechanisms that allow specific regulation of Pax7 remain largely unknown. Here, 
we report for the first time that Pax7 is regulated by SUMOylation. We identify 
the interaction of Pax7 with Ubc9, the SUMO conjugating enzyme, and reveal that 
SUMOylation machinery is enriched in neural crest precursors and plays a 
critical role in NC development. We demonstrate that Pax7 becomes SUMOylated and 
identify an essential role for lysine 85 (K85) in Pax7-SUMOylation. Despite high 
conservation surrounding K85 amongst Pax genes, we were unable to identify 
SUMOylation of other Pax proteins tested, including Pax3. Using a 
non-SUMOylatable Pax7 variant (K85 X R), we demonstrate that SUMOylation is 
essential for the function of Pax7 in neural crest development, C2C12 myogenic 
differentiation, and transcriptional transactivation. Our study provides new 
mechanistic insight into the molecular regulation of Pax7's function by 
SUMOylation in neural crest and muscle development.