Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter.
Previous work has established that the melanocyte-specific tyrosinase-related protein-1 (TRP-1) promoter is regulated positively by the microphthalmia-associated transcription factor Mitf, acting through the conserved M box and negatively by the T-box factor Tbx2, which can bind two "melanocyte-specific elements" termed the MSEu and MSEi. Both the MSEu and MSEi, which share a 6-base pair GTGTGA consensus, are also recognized by a previously unidentified melanocyte-specific factor, MSF. Here we show using a combination of DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that MSF is indistinguishable from Pax3, a paired homeodomain transcription factor implicated genetically in melanocyte development and the regulation of the Mitf promoter. Consistent with Pax3 being able to bind the TRP-1 promoter, Pax3 is expressed in melanocytes and melanomas, and TRP-1 promoter activity is up-regulated by Pax3. The results identify a novel role for Pax3 in the expression of TRP-1, and the potential role of Pax3 in the melanocyte lineage is discussed.
Galibert
M D
MD
Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, RH8 OTL, United Kingdom.
Yavuzer
U
U
Dexter
T J
TJ
Goding
C R
CR
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1