1275 A mutual repression between MITF and neural transcription factors specifies the fate of schwann cell precursors

Melanocytes are derived from neural crest cells, which also differentiate into neurons, glial bone/cartilage and smooth muscles. Melanocyte-inducing transcription factor (MITF) promotes melanocyte development differentiation through activating pigment genes. Since MITF activates most of its target genes represses a few them, we aimed to characterize repressed by MITF. By using RNA sequencing chromatin immunoprecipitation sequencing, found that (neuronal/Schwann cell) genes, including repressors such as FOXD3 (bound MITF) POU3F2 (not bound MITF), were highly enriched in induced knockdown (KD) human primary melanocytes. double attenuates NGFR induction compared with MITF-KD alone, suggesting directly repressing factors. melanocytes Schwann cell precursors, hypothesized number is increased Mitf-mutant mice sciatic nerves larger than those wild-type (p < 0.01). We ID1, gene MITF, was expressed ∼40% desmoplastic (low-MITF) melanomas but not nevi conventional 0.05). Our results suggest (1) specifies only specific protecting precursors differentiating neurons/Schwann cells genes; (2) mutual repression between factors controls precursor fate.