Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a.
Microphthalmia-associated transcription factor (Mitf) plays a critical role in the development of neural crest-derived melanocytes. Here, we show that exogenously added Wnt-3a protein, an intercellular signaling molecule, up-regulates the expression of endogenous melanocyte-specific Mitf (Mitf-M) mRNA in cultured melanocytes. The melanocyte-specific promoter of the human MITF gene (MITF-M promoter) contains a functional LEF-1-binding site, which is bound in vitro by LEF-1 and confers the preferential expression on a reporter gene in melanocytes and melanoma cells, as judged by the transient transfection assays. Moreover, the LEF-1-binding site is required for the transactivation of a reporter gene by LEF-1, beta-catenin, or their combination. Exogenously added Wnt-3a protein also transactivates the MITF-M promoter via the LEF-1-binding site; this activation was abolished when a dominant-negative form of LEF-1 was coexpressed. These results suggest that Wnt-3a signaling recruits beta-catenin and LEF-1 to the LEF-1-binding site of the MITF-M promoter. Therefore, the present study identifies Mitf-M/MITF-M as a direct target of Wnt signaling.
Takeda
K
K
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Yasumoto
K
K
Takada
R
R
Takada
S
S
Watanabe
K
K
Udono
T
T
Saito
H
H
Takahashi
K
K
Shibahara
S
S
D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics; D005124:Eye Abnormalities / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D011506:Proteins; D014157:Transcription Factors; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D004247:DNA