Gpnmbis a melanoblast-expressed, MITF-dependent gene

Expression profile analysis clusters Gpnmbwith known pigment genes, Tyrp1, Dct, and Si. During development, Gpnmbis expressed in a pattern similar to Mitf, Dctand Siwith expression vastly reduced in Mitfmutant animals. Unlike Dctand Si, Gpnmbremains expressed in a discrete population of caudal melanoblasts in Sox10-deficient embryos. To understand the transcriptional regulation of Gpnmbwe performed a whole genome annotation of 2,460,048 consensus MITF binding sites, and cross-referenced this with evolutionarily conserved genomic sequences at the GPNMB locus. One conserved element, GPNMB-MCS3, contained two MITF consensus sites, significantly increased luciferase activity in melanocytes and was sufficient to drive expression in melanoblasts in vivo. Deletion of the 5'-most MITF consensus site dramatically reduced enhancer activity indicating a significant role for this site in Gpnmbtranscriptional regulation. Future analysis of the Gpnmblocus will provide insight into the transcriptional regulation of melanocytes, and Gpnmbexpression can be used as a marker for analyzing melanocyte development and disease progression.