Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter

Previous work has established that the melanocyte-specific tyrosinase-relat ed protein-1 (TRP-1) promoter is regulated positively by the microphthalmia -associated transcription factor Mitf, acting through the conserved M box a nd negatively by the T-box factor Tbx2, which can bind two "melanocyte-spec ific elements" termed the MSEu and MSEi. Both the MSEu and MSEi, which shar e a 6-base pair GTGTGA consensus, are also recognized by a previously unide ntified melanocyte-specific factor, MSF. Here we show using a combination o f DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that M SF is indistinguishable from Pax3, a paired homeodomain transcription facto r implicated genetically in melanocyte development and the regulation of th e Mitf promoter. Consistent with Pax3 being able to bind the TRP-1 promoter , Pax3 is expressed in melanocytes and melanomas, and TRP-I promoter activi ty is up-regulated by Pax3. The results identify a novel role for Pax3 in t he expression of TRP-1, and the potential role of Pax3 in the melanocyte li neage is discussed.