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.