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Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene.

Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.

ABSTRACT

Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and is specifically expressed in differentiated melanocytes. We have identified the enhancer element in the 5'-flanking region of the human tyrosinase gene that is responsible for its pigment cell-specific transcription and have termed it tyrosinase distal element (TDE) (positions -1861 to -1842). Transient expression assays showed that TDE confers efficient expression of a firefly luciferase reporter gene linked to the tyrosinase gene promoter in MeWo pigmented melanoma cells but not in HeLa cells, which do not express tyrosinase. TDE was specifically bound by nuclear proteins of MeWo and HeLa cells, the binding properties of which were indistinguishable in gel mobility shift assays. TDE contains the CATGTG motif in its center, and mutation analysis indicates that the CA dinucleotides of this motif are crucial for protein binding and pigment cell-specific enhancer function. The CATGTG motif is consistent with the consensus sequence recognized by a large family of transcription factors with a basic helix-loop-helix structure, which prompted us to examine the possible involvement of a ubiquitous transcription factor, USF, and a novel factor, microphthalmia-associated transcription factor (MITF), recently cloned as the human homolog of the mouse microphthalmia (mi) gene product. The mi phenotype is associated with a mutant mi locus and characterized by small eyes and loss of melanin pigments. Both USF and MITF are predicted to contain a basic helix-loop-helix structure and a leucine zipper structure. We provide evidence that USF binds to TDE, whereas we were unable to detect the DNA-binding activity of MITF. Transient coexpression assays showed that MITF specifically transactivates the promoter activity of the tyrosinase gene through the CATGTG motif of TDE but not the promoter of the ubiquitously expressed heme oxygenase gene, while USF is able to activate both promoters. These results indicate that MITF is a cell-type-specific factor that is capable of activating transcription of the tyrosinase gene.

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• Du, J., Fisher, D. E. (2002). Identification of Aim-1 as the underwhite Mouse Mutant and Its Transcriptional Regulation by MITF. J. Biol. Chem. 277: 402-406 [Abstract] [Full Text]  
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• Hou, L, Panthier, J., Arnheiter, H (2000). Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF. Development 127: 5379-5389 [Abstract]  
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• Takeda, K., Takemoto, C., Kobayashi, I., Watanabe, A., Nobukuni, Y., Fisher, D. E., Tachibana, M. (2000). Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance. Hum Mol Genet 9: 125-132 [Abstract] [Full Text]  
• King, R., Weilbaecher, K. N., McGill, G., Cooley, E., Mihm, M., Fisher, D. E. (1999). Microphthalmia Transcription Factor : A Sensitive and Specific Melanocyte Marker for MelanomaDiagnosis. Am. J. Pathol. 155: 731-738 [Abstract] [Full Text]  
• Planque, N., Turque, N., Opdecamp, K., Bailly, M., Martin, P., Saule, S. (1999). Expression of the Microphthalmia-associated Basic Helix-Loop-Helix Leucine Zipper Transcription Factor Miin Avian Neuroretina Cells Induces aPigmented Phenotype. Cell Growth Differ. 10: 525-536 [Abstract] [Full Text]  
• Jippo, T., Lee, Y.-M., Katsu, Y., Tsujino, K., Morii, E., Kim, D.-K., Kim, H.-M., Kitamura, Y. (1999). Deficient Transcription of Mouse Mast Cell Protease 4 Gene in Mutant Mice of mi/mi Genotype. Blood 93: 1942-1950 [Abstract] [Full Text]  
• Ito, A., Morii, E., Kim, D.-K., Kataoka, T. R., Jippo, T., Maeyama, K., Nojima, H., Kitamura, Y. (1999). Inhibitory Effect of the Transcription Factor Encoded by the mi Mutant Allele in Cultured Mast Cells of Mice. Blood 93: 1189-1196 [Abstract] [Full Text]  
• Price, E. R., Horstmann, M. A., Wells, A. G., Weilbaecher, K. N., Takemoto, C. M., Landis, M. W., Fisher, D. E. (1998). alpha -Melanocyte-stimulating Hormone Signaling Regulates Expression of microphthalmia, a Gene Deficient in Waardenburg Syndrome. J. Biol. Chem. 273: 33042-33047 [Abstract] [Full Text]  
• Aksan, I., Goding, C. R. (1998). Targeting the Microphthalmia Basic Helix-Loop-Helix-Leucine Zipper Transcription Factor to a Subset of E-Box Elements In Vitro and In Vivo. Mol. Cell. Biol. 18: 6930-6938 [Abstract] [Full Text]  
• Carreira, S., Dexter, T. J., Yavuzer, U., Easty, D. J., Goding, C. R. (1998). Brachyury-Related Transcription Factor Tbx2 and Repression of the Melanocyte-Specific TRP-1 Promoter. Mol. Cell. Biol. 18: 5099-5108 [Abstract] [Full Text]  
• Bertolotto, C., Abbe, P., Hemesath, T. J., Bille, K., Fisher, D. E., Ortonne, J.-P., Ballotti, R. (1998). Microphthalmia Gene Product as a Signal Transducer in cAMP-Induced Differentiation of Melanocytes. J. Cell Biol. 142: 827-835 [Abstract] [Full Text]  
• Aberdam, E., Bertolotto, C., Sviderskaya, E. V., de Thillot, V., Hemesath, T. J., Fisher, D. E., Bennett, D. C., Ortonne, J.-P., Ballotti, R. (1998). Involvement of Microphthalmia in the Inhibition of Melanocyte Lineage Differentiation and of Melanogenesis by Agouti Signal Protein. J. Biol. Chem. 273: 19560-19565 [Abstract] [Full Text]  
• Price, E. R., Ding, H.-F., Badalian, T., Bhattacharya, S., Takemoto, C., Yao, T.-P., Hemesath, T. J., Fisher, D. E. (1998). Lineage-specific Signaling in Melanocytes. c-Kit STIMULATION RECRUITS p300/CBP TO MICROPHTHALMIA. J. Biol. Chem. 273: 17983-17986 [Abstract] [Full Text]  
• Furumura, M., Sakai, C., Potterf, S. B., Vieira, W. D., Barsh, G. S., Hearing, V. J. (1998). Characterization of genes modulated during pheomelanogenesis using differential display. Proc. Natl. Acad. Sci. USA 95: 7374-7378 [Abstract] [Full Text]  
• Ito, A., Morii, E., Maeyama, K., Jippo, T., Kim, D.-K., Lee, Y.-M., Ogihara, H., Hashimoto, K., Kitamura, Y., Nojima, H. (1998). Systematic Method to Obtain Novel Genes That Are Regulated by mi Transcription Factor: Impaired Expression of Granzyme B and Tryptophan Hydroxylase in mi/mi Cultured Mast Cells. Blood 91: 3210-3221 [Abstract] [Full Text]  
• Weilbaecher, K. N., Hershey, C. L., Takemoto, C. M., Horstmann, M. A., Hemesath, T. J., Tashjian, A. H. Jr., Fisher, D. E. (1998). Age-resolving Osteopetrosis: A Rat Model Implicating Microphthalmia and the Related Transcription Factor TFE3. J. Exp. Med. 187: 775-785 [Abstract] [Full Text]  
• Diaz, R. M., Eisen, T., Hart, I. R., Vile, R. G. (1998). Exchange of Viral Promoter/Enhancer Elements with Heterologous Regulatory Sequences Generates Targeted Hybrid Long Terminal Repeat Vectors for Gene Therapy of Melanoma. J. Virol. 72: 789-795 [Abstract] [Full Text]  
• Morii, E., Jippo, T., Tsujimura, T., Hashimoto, K., Kim, D.-K., Lee, Y.-M., Ogihara, H., Tsujino, K., Kim, H.-M., Kitamura, Y. (1997). Abnormal Expression of Mouse Mast Cell Protease 5 Gene in Cultured Mast Cells Derived From Mutant mi/mi Mice. Blood 90: 3057-3066 [Abstract] [Full Text]  
• Jippo, T., Morii, E., Tsujino, K., Tsujimura, T., Lee, Y.-M., Kim, D.-K., Matsuda, H., Kim, H.-M., Kitamura, Y. (1997). Involvement of Transcription Factor Encoded by the Mouse mi Locus (MITF ) in Expression of p75 Receptor of Nerve Growth Factor in Cultured Mast Cells of Mice. Blood 90: 2601-2608 [Abstract] [Full Text]  
• Yasumoto, K.-i., Yokoyama, K., Takahashi, K., Tomita, Y., Shibahara, S. (1997). Functional Analysis of Microphthalmia-associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes. J. Biol. Chem. 272: 503-509 [Abstract] [Full Text]  
• Takeda, K., Yasumoto, K.-i., Takada, R., Takada, S., Watanabe, K.-i., Udono, T., Saito, H., Takahashi, K., Shibahara, S. (2000). Induction of Melanocyte-specific Microphthalmia-associated Transcription Factor by Wnt-3a. J. Biol. Chem. 275: 14013-14016 [Abstract] [Full Text]  
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• Furumura, M., Potterf, S. B., Toyofuku, K., Matsunaga, J., Muller, J., Hearing, V. J. (2001). Involvement of ITF2 in the Transcriptional Regulation of Melanogenic Genes. J. Biol. Chem. 276: 28147-28154 [Abstract] [Full Text]  
• Planque, N., Leconte, L., Coquelle, F. M., Martin, P., Saule, S. (2001). Specific Pax-6/Microphthalmia Transcription Factor Interactions Involve Their DNA-binding Domains and Inhibit Transcriptional Properties of Both Proteins. J. Biol. Chem. 276: 29330-29337 [Abstract] [Full Text]