RESEARCH ARTICLE LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

TYR, DCT andMITF are three important genes involved in maintaining the mature pheno-type and producing melanin; they therefore participate in neural crest cell development into melanocytes. Previous studies have revealed that the Wnt signaling factor lymphoid enhancer-binding factor (LEF-1) can enhance DCT andMITF gene expression. However, whether LEF-1 also affects TYR gene expression remains unclear. In the present study, we found that LEF-1 regulated TYR transcription in vitro. LEF-1 overexpression increased TYR gene promoter activity, whereas LEF-1 knockdown by RNA interference significantly decreased TYR expression. Moreover, the core GTTTGAT sequence (-56 to-50) within the TYR promoter is essential for the effect of LEF-1 on TYR expression, and chromatin immu-noprecipitation (ChIP) assay indicated that endogenous LEF-1 interacts with the TYR pro-moter. In addition, we observed a synergistic transactivation of the TYR promoter by LEF-1 and MITF. These data suggest that Wnt signaling plays an important role in regulating mela-nocyte development and differentiation