This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carreira, S.
Right arrow Articles by Goding, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carreira, S.
Right arrow Articles by Goding, C. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 1998, p. 5099-5108, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Brachyury-Related Transcription Factor Tbx2 and Repression of the Melanocyte-Specific TRP-1 Promoter

S. Carreira, T. J. Dexter,dagger U. Yavuzer,Dagger D. J. Easty,§ and C. R. Goding*

Eukaryotic Transcription Laboratory, Marie Curie Research Institute, Oxted, Surrey RH8 0TL, United Kingdom

Received 13 March 1998/Returned for modification 5 May 1998/Accepted 16 June 1998

Previous work has demonstrated that two key melanocyte-specific elements termed the MSEu and MSEi play critical roles in the expression of the melanocyte-specific tyrosinase-related protein 1 (TRP-1) promoter. Both the MSEu and MSEi, located at position -237 and at the initiator, respectively, bind a melanocyte-specific factor termed MSF but are also recognized by a previously uncharacterized repressor, since mutations affecting either of these elements result in strong up-regulation of TRP-1 promoter activity in melanoma cells. Here we demonstrate that repression mediated by the MSEu and MSEi also operates in melanocytes. We also report that both the MSEu and MSEi are recognized by the brachyury-related transcription factor Tbx2, a member of the recently described T-box family, and that Tbx2 is expressed in melanocyte and melanoblast cell lines but not in melanoblast precursor cells. Although Tbx2 and MSF each recognize the TRP-1 MSEu and MSEi motifs, it is binding by Tbx-2, not binding by MSF, that correlates with repression. Several lines of evidence tend to point to the brachyury-related transcription factor Tbx2 as being the repressor of TRP-1 expression: both the MSEu and MSEi bind Tbx2, and mutations in either element that result in derepression of the TRP-1 promoter diminish binding by Tbx2; the TRP-1 promoter, but not the tyrosinase, microphthalmia, or glyceraldehyde-3-phosphate dehydrogenase (G3PDH) promoter, is repressed by Tbx2 in cotransfection assays; a high-affinity consensus brachyury/Tbx2-binding site is able to constitutively repress expression of the heterologous IE110 promoter; and a low-affinity brachyury/Tbx2 binding site is able to mediate Tbx2-dependent repression of the G3PDH promoter. Although we cannot rule out the presence of an additional, as yet unidentified factor playing a role in the negative regulation of TRP-1 in vivo, the evidence presented here suggests that Tbx2 most likely is the previously unidentified repressor of TRP-1 expression and as such is likely to represent the first example of transcriptional repression by a T-box family member.

* Corresponding author. Mailing address: Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom. Phone: (44) 1883 722306. Fax: (44) 1883 714375. E-mail: c.goding{at}mcri.ac.uk.

dagger Present address: National Institute for Medical Research, London NW7 1AA, United Kingdom.

Dagger Present address: Molecular Biology Department, Bilkent University, 06533 Bilkent, Ankara, Turkey.

§ Present address: Department of Pathology, University College Dublin, Dublin, Ireland.

Molecular and Cellular Biology, September 1998, p. 5099-5108, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Teng, H., Ballim, R. D., Mowla, S., Prince, S. (2009). Phosphorylation of Histone H3 by Protein Kinase C Signaling Plays a Critical Role in the Regulation of the Developmentally Important TBX2 Gene. J. Biol. Chem. 284: 26368-26376 [Abstract] [Full Text]  
  • Sviderskaya, E. V., Easty, D. J., Lawrence, M. A., Sanchez, D. P., Negulyaev, Y. A., Patel, R. H., Anand, P., Korchev, Y. E., Bennett, D. C. (2009). Functional neurons and melanocytes induced from immortal lines of postnatal neural crest-like stem cells. FASEB J. 23: 3179-3192 [Abstract] [Full Text]  
  • Rodriguez, M., Aladowicz, E., Lanfrancone, L., Goding, C. R. (2008). Tbx3 Represses E-Cadherin Expression and Enhances Melanoma Invasiveness. Cancer Res. 68: 7872-7881 [Abstract] [Full Text]  
  • Nikolova, G., Sinsheimer, J. S., Eicher, E. M., Vilain, E. (2008). The Chromosome 11 Region From Strain 129 Provides Protection From Sex Reversal in XYPOS Mice. Genetics 179: 419-427 [Abstract] [Full Text]  
  • Abrahams, A., Mowla, S., Parker, M. I., Goding, C. R., Prince, S. (2008). UV-mediated Regulation of the Anti-senescence Factor Tbx2. J. Biol. Chem. 283: 2223-2230 [Abstract] [Full Text]  
  • Gross, J. M., Dowling, J. E. (2005). Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina. Proc. Natl. Acad. Sci. USA 102: 4371-4376 [Abstract] [Full Text]  
  • Vance, K. W., Carreira, S., Brosch, G., Goding, C. R. (2005). Tbx2 Is Overexpressed and Plays an Important Role in Maintaining Proliferation and Suppression of Senescence in Melanomas. Cancer Res. 65: 2260-2268 [Abstract] [Full Text]  
  • Slominski, A., Tobin, D. J., Shibahara, S., Wortsman, J. (2004). Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation. Physiol. Rev. 84: 1155-1228 [Abstract] [Full Text]  
  • Goodall, J., Wellbrock, C., Dexter, T. J., Roberts, K., Marais, R., Goding, C. R. (2004). The Brn-2 Transcription Factor Links Activated BRAF to Melanoma Proliferation. Mol. Cell. Biol. 24: 2923-2931 [Abstract] [Full Text]  
  • Prince, S., Carreira, S., Vance, K. W., Abrahams, A., Goding, C. R. (2004). Tbx2 Directly Represses the Expression of the p21WAF1 Cyclin-Dependent Kinase Inhibitor. Cancer Res. 64: 1669-1674 [Abstract] [Full Text]  
  • Lee, D. U., Avni, O., Chen, L., Rao, A. (2004). A Distal Enhancer in the Interferon-{gamma} (IFN-{gamma}) Locus Revealed by Genome Sequence Comparison. J. Biol. Chem. 279: 4802-4810 [Abstract] [Full Text]  
  • Bejar, J., Hong, Y., Schartl, M. (2003). Mitf expression is sufficient to direct differentiation of medaka blastula derived stem cells to melanocytes. Development 130: 6545-6553 [Abstract] [Full Text]  
  • Piotrowski, T., Ahn, D.-g., Schilling, T. F., Nair, S., Ruvinsky, I., Geisler, R., Rauch, G.-J., Haffter, P., Zon, L. I., Zhou, Y., Foott, H., Dawid, I. B., Ho, R. K. (2003). The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development 130: 5043-5052 [Abstract] [Full Text]  
  • Davenport, T. G., Jerome-Majewska, L. A., Papaioannou, V. E. (2003). Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development 130: 2263-2273 [Abstract] [Full Text]  
  • Pulichino, A.-M., Vallette-Kasic, S., Tsai, J. P.-Y., Couture, C., Gauthier, Y., Drouin, J. (2003). Tpit determines alternate fates during pituitary cell differentiation. Genes Dev. 17: 738-747 [Abstract] [Full Text]  
  • Kwang, S. J., Brugger, S. M., Lazik, A., Merrill, A. E., Wu, L.-Y., Liu, Y.-H., Ishii, M., Sangiorgi, F. O., Rauchman, M., Sucov, H. M., Maas, R. L., Maxson, R. E. Jr. (2003). Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest. Development 129: 527-538 [Abstract] [Full Text]  
  • Niles, R. M. (2003). Vitamin A (Retinoids) Regulation of Mouse Melanoma Growth and Differentiation. J. Nutr. 133: 282S-286 [Abstract] [Full Text]  
  • Braybrook, C., Lisgo, S., Doudney, K., Henderson, D., Marcano, A. C. B., Strachan, T., Patton, M. A., Villard, L., Moore, G. E., Stanier, P., Lindsay, S. (2002). Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients. Hum Mol Genet 11: 2793-2804 [Abstract] [Full Text]  
  • Fang, D., Tsuji, Y., Setaluri, V. (2002). Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF. Nucleic Acids Res 30: 3096-3106 [Abstract] [Full Text]  
  • Lingbeek, M. E., Jacobs, J. J. L., van Lohuizen, M. (2002). The T-box Repressors TBX2 and TBX3 Specifically Regulate the Tumor Suppressor Gene p14ARF via a Variant T-site in the Initiator. J. Biol. Chem. 277: 26120-26127 [Abstract] [Full Text]  
  • Habets, P. E.M.H., Moorman, A. F.M., Clout, D. E.W., van Roon, M. A., Lingbeek, M., van Lohuizen, M., Campione, M., Christoffels, V. M. (2002). Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes Dev. 16: 1234-1246 [Abstract] [Full Text]  
  • Kusch, T., Storck, T., Walldorf, U., Reuter, R. (2002). Brachyury proteins regulate target genes through modular binding sites in a cooperative fashion. Genes Dev. 16: 518-529 [Abstract] [Full Text]  
  • Brummelkamp, T. R., Kortlever, R. M., Lingbeek, M., Trettel, F., MacDonald, M. E., van Lohuizen, M., Bernards, R. (2002). TBX-3, the Gene Mutated in Ulnar-Mammary Syndrome, Is a Negative Regulator of p19ARF and Inhibits Senescence. J. Biol. Chem. 277: 6567-6572 [Abstract] [Full Text]  
  • Szeto, D. P., Griffin, K. J. P., Kimelman, D. (2002). hrT is required for cardiovascular development in zebrafish. Development 129: 5093-5101 [Abstract] [Full Text]  
  • Carlson, H., Ota, S., Campbell, C. E., Hurlin, P. J. (2001). A dominant repression domain in Tbx3 mediates transcriptional repression and cell immortalization: relevance to mutations in Tbx3 that cause ulnar-mammary syndrome. Hum Mol Genet 10: 2403-2413 [Abstract] [Full Text]  
  • Ghosh, T. K., Packham, E. A., Bonser, A. J., Robinson, T. E., Cross, S. J., Brook, J. D. (2001). Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. Hum Mol Genet 10: 1983-1994 [Abstract] [Full Text]  
  • Liu, J., Lin, C., Gleiberman, A., Ohgi, K. A., Herman, T., Huang, H.-P., Tsai, M.-J., Rosenfeld, M. G. (2001). Tbx19, a tissue-selective regulator of POMC gene expression. Proc. Natl. Acad. Sci. USA 10.1073/pnas.141234898v1 [Abstract] [Full Text]  
  • Goding, C. R. (2000). Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev. 14: 1712-1728 [Full Text]  
  • Hyde, C., Old, R. (2000). Regulation of the early expression of the Xenopus nodal-related 1 gene, Xnr1. Development 127: 1221-1229 [Abstract]  
  • Galibert, M.-D., Yavuzer, U., Dexter, T. J., Goding, C. R. (1999). Pax3 and Regulation of the Melanocyte-specific Tyrosinase-related Protein-1 Promoter. J. Biol. Chem. 274: 26894-26900 [Abstract] [Full Text]  
  • He, M.-l., Wen, L., Campbell, C. E., Wu, J. Y., Rao, Y. (1999). Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome. Proc. Natl. Acad. Sci. USA 96: 10212-10217 [Abstract] [Full Text]  
  • Casey, E., Tada, M, Fairclough, L, Wylie, C., Heasman, J, Smith, J. (1999). Bix4 is activated directly by VegT and mediates endoderm formation in Xenopus development. Development 126: 4193-4200 [Abstract]  
  • Carreira, S., Liu, B., Goding, C. R. (2000). The Gene Encoding the T-box Factor Tbx2 Is a Target for the Microphthalmia-associated Transcription Factor in Melanocytes. J. Biol. Chem. 275: 21920-21927 [Abstract] [Full Text]  
  • Lee, M., Goodall, J., Verastegui, C., Ballotti, R., Goding, C. R. (2000). Direct Regulation of the Microphthalmia Promoter by Sox10 Links Waardenburg-Shah Syndrome (WS4)-associated Hypopigmentation and Deafness to WS2. J. Biol. Chem. 275: 37978-37983 [Abstract] [Full Text]  
  • Liu, J., Lin, C., Gleiberman, A., Ohgi, K. A., Herman, T., Huang, H.-P., Tsai, M.-J., Rosenfeld, M. G. (2001). Tbx19, a tissue-selective regulator of POMC gene expression. Proc. Natl. Acad. Sci. USA 98: 8674-8679 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»