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 Postigo, A. A.
Right arrow Articles by Dean, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Postigo, A. A.
Right arrow Articles by Dean, D. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 1999, p. 7255-7263, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

zfh-1, the Drosophila Homologue of ZEB, Is a Transcriptional Repressor That Regulates Somatic Myogenesis

Antonio A. Postigo,1 Ellen Ward,2 James B. Skeath,2 and Douglas C. Dean1,*

Division of Molecular Oncology1 and Department of Genetics,2 Washington University School of Medicine, St. Louis, Missouri 63110

Received 13 April 1999/Returned for modification 25 May 1999/Accepted 15 June 1999

zfh-1 is a member of the zfh family of proteins, which all contain zinc finger and homeodomains. The roles and mechanisms of action of most family members are still unclear. However, we have shown previously that another member of the family, the vertebrate ZEB protein, is a transcriptional repressor that binds E box sequences and inhibits myotube formation in cell culture assays. zfh-1 is downregulated in Drosophila embryos prior to myogenesis. Embryos with zfh-1 loss-of-function mutation show alterations in the number and position of embryonic somatic muscles, suggesting that zfh-1 could have a regulatory role in myogenesis. However, nothing is known about the nature or mechanism of action of zfh-1. Here, we demonstrate that zfh-1 is a transcription factor that binds E box sequences and acts as an active transcriptional repressor. When zfh-1 expression was maintained in the embryo beyond its normal temporal pattern of downregulation, the differentiation of somatic but not visceral muscle was blocked. One potential target of zfh-1 in somatic myogenesis could be the myogenic factor mef2. mef2 is known to be regulated by the transcription factor twist, and we show here that zfh-1 binds to sites in the mef2 upstream regulatory region and inhibits twist transcriptional activation. Even though there is little sequence similarity in the repressor domains of ZEB and zfh-1, we present evidence that zfh-1 is the functional homologue of ZEB and that the role of these proteins in myogenesis is conserved from Drosophila to mammals.

* Corresponding author. Mailing address: Washington University School of Medicine, Division of Molecular Oncology, Campus Box 8069, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-8989. Fax: (314) 747-2797. E-mail: ddean{at}im.wustl.edu.

Molecular and Cellular Biology, October 1999, p. 7255-7263, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wang, J., Lee, S., Teh, C. E.-Y., Bunting, K., Ma, L., Shannon, M. F. (2009). The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells. Int Immunol 21: 227-235 [Abstract] [Full Text]  
  • Krejci, A., Bernard, F., Housden, B. E., Collins, S., Bray, S. J. (2009). Direct Response to Notch Activation: Signaling Crosstalk and Incoherent Logic. Sci Signal 2: ra1-ra1 [Abstract] [Full Text]  
  • Miller, M. M., Jarosinski, K. W., Schat, K. A. (2008). Negative modulation of the chicken infectious anemia virus promoter by COUP-TF1 and an E box-like element at the transcription start site binding {delta}EF1. J. Gen. Virol. 89: 2998-3003 [Abstract] [Full Text]  
  • Zhao, M., Szafranski, P., Hall, C. A., Goode, S. (2008). Basolateral Junctions Utilize Warts Signaling to Control Epithelial-Mesenchymal Transition and Proliferation Crucial For Migration and Invasion of Drosophila Ovarian Epithelial Cells. Genetics 178: 1947-1971 [Abstract] [Full Text]  
  • Johnson, A. N., Burnett, L. A., Sellin, J., Paululat, A., Newfeld, S. J. (2007). Defective Decapentaplegic Signaling Results in Heart Overgrowth and Reduced Cardiac Output in Drosophila. Genetics 176: 1609-1624 [Abstract] [Full Text]  
  • Spoelstra, N. S., Manning, N. G., Higashi, Y., Darling, D., Singh, M., Shroyer, K. R., Broaddus, R. R., Horwitz, K. B., Richer, J. K. (2006). The Transcription Factor ZEB1 Is Aberrantly Expressed in Aggressive Uterine Cancers.. Cancer Res. 66: 3893-3902 [Abstract] [Full Text]  
  • Pena, C., Garcia, J. M., Silva, J., Garcia, V., Rodriguez, R., Alonso, I., Millan, I., Salas, C., de Herreros, A. G., Munoz, A., Bonilla, F. (2005). E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations. Hum Mol Genet 14: 3361-3370 [Abstract] [Full Text]  
  • Baker, P. W., Tanaka, K. K. K., Klitgord, N., Cripps, R. M. (2005). Adult Myogenesis in Drosophila melanogaster Can Proceed Independently of Myocyte Enhancer Factor-2. Genetics 170: 1747-1759 [Abstract] [Full Text]  
  • Wacker, I., Schwarz, V., Hedgecock, E. M., Hutter, H. (2003). zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development 130: 3795-3805 [Abstract] [Full Text]  
  • Musikacharoen, T., Yoshikai, Y., Matsuguchi, T. (2003). Histone Acetylation and Activation of cAMP-response Element-binding Protein Regulate Transcriptional Activation of MKP-M in Lipopolysaccharide-stimulated Macrophages. J. Biol. Chem. 278: 9167-9175 [Abstract] [Full Text]  
  • Butler, M. J., Jacobsen, T. L., Cain, D. M., Jarman, M. G., Hubank, M., Whittle, J. R. S., Phillips, R., Simcox, A. (2003). Discovery of genes with highly restricted expression patterns in the Drosophila wing disc using DNA oligonucleotide microarrays. Development 130: 659-670 [Abstract] [Full Text]  
  • Kraus, R. J., Perrigoue, J. G., Mertz, J. E. (2002). ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus. J. Virol. 77: 199-207 [Abstract] [Full Text]  
  • Fontemaggi, G., Gurtner, A., Strano, S., Higashi, Y., Sacchi, A., Piaggio, G., Blandino, G. (2001). The Transcriptional Repressor ZEB Regulates p73 Expression at the Crossroad between Proliferation and Differentiation. Mol. Cell. Biol. 21: 8461-8470 [Abstract] [Full Text]  
  • Touitou, R., Hickabottom, M., Parker, G., Crook, T., Allday, M. J. (2001). Physical and Functional Interactions between the Corepressor CtBP and the Epstein-Barr Virus Nuclear Antigen EBNA3C. J. Virol. 75: 7749-7755 [Abstract] [Full Text]  
  • Zhang, Q., Yao, H., Vo, N., Goodman, R. H. (2000). Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP. Proc. Natl. Acad. Sci. USA 10.1073/pnas.011283598v1 [Abstract] [Full Text]  
  • Postigo, A. A., Dean, D. C. (2000). Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors. Proc. Natl. Acad. Sci. USA 97: 6391-6396 [Abstract] [Full Text]  
  • Ward, E., Skeath, J. (2000). Characterization of a novel subset of cardiac cells and their progenitors in the Drosophila embryo. Development 127: 4959-4969 [Abstract]  
  • Postigo, A. A., Dean, D. C. (1999). Independent Repressor Domains in ZEB Regulate Muscle and T-Cell Differentiation. Mol. Cell. Biol. 19: 7961-7971 [Abstract] [Full Text]  
  • Zhang, Q., Yao, H., Vo, N., Goodman, R. H. (2000). Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP. Proc. Natl. Acad. Sci. USA 97: 14323-14328 [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»