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 Wilson-Rawls, J.
Right arrow Articles by Olson, E. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilson-Rawls, J.
Right arrow Articles by Olson, E. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 1999, p. 2853-2862, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activated Notch Inhibits Myogenic Activity of the MADS-Box Transcription Factor Myocyte Enhancer Factor 2C

Jeanne Wilson-Rawls,dagger Jeffery D. Molkentin,Dagger Brian L. Black,§ and Eric N. Olson*

Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9148

Received 17 June 1998/Returned for modification 5 August 1998/Accepted 15 December 1998

Skeletal muscle gene expression is dependent on combinatorial associations between members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors and the myocyte enhancer factor 2 (MEF2) family of MADS-box transcription factors. The transmembrane receptor Notch interferes with the muscle-inducing activity of myogenic bHLH proteins, and it has been suggested that this inhibitory activity of Notch is directed at an essential cofactor that recognizes the DNA binding domains of the myogenic bHLH proteins. Given that MEF2 proteins interact with the DNA binding domains of myogenic bHLH factors to cooperatively regulate myogenesis, we investigated whether members of the MEF2 family might serve as targets for the inhibitory effects of Notch on myogenesis. We show that a constitutively activated form of Notch specifically blocks DNA binding by MEF2C, as well as its ability to cooperate with MyoD and myogenin to activate myogenesis. Responsiveness to Notch requires a 12-amino-acid region of MEF2C immediately adjacent to the DNA binding domain that is unique to this MEF2 isoform. Two-hybrid assays and coimmunoprecipitations show that this region of MEF2C interacts directly with the ankyrin repeat region of Notch. These findings reveal a novel mechanism for Notch-mediated inhibition of myogenesis and demonstrate that the Notch signaling pathway can discriminate between different members of the MEF2 family.

* Corresponding author. Mailing address: Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd., Dallas, TX 75235-9148. Phone: (214) 648-1187. Fax: (214) 648-1196. E-mail: eolson{at}hamon.swmed.edu.

dagger Present address: Department of Biology, Arizona State University, Tempe, AZ 85287-1501.

Dagger Present address: Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, OH 45229-3039.

§ Present address: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143.

Molecular and Cellular Biology, April 1999, p. 2853-2862, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sun, D., Li, H., Zolkiewska, A. (2008). The role of Delta-like 1 shedding in muscle cell self-renewal and differentiation. J. Cell Sci. 121: 3815-3823 [Abstract] [Full Text]  
  • Waters, A. M., Wu, M. Y.J., Onay, T., Scutaru, J., Liu, J., Lobe, C. G., Quaggin, S. E., Piscione, T. D. (2008). Ectopic Notch Activation in Developing Podocytes Causes Glomerulosclerosis. J. Am. Soc. Nephrol. 19: 1139-1157 [Full Text]  
  • Ben-Yair, R., Kalcheim, C. (2008). Notch and bone morphogenetic protein differentially act on dermomyotome cells to generate endothelium, smooth, and striated muscle. JCB 180: 607-618 [Abstract] [Full Text]  
  • Laky, K., Fowlkes, B.J. (2007). Presenilins regulate {alpha}{beta} T cell development by modulating TCR signaling. JEM 204: 2115-2129 [Abstract] [Full Text]  
  • Chandran, R., Knobloch, T. J., Anghelina, M., Agarwal, S. (2007). Biomechanical signals upregulate myogenic gene induction in the presence or absence of inflammation. Am. J. Physiol. Cell Physiol. 293: C267-C276 [Abstract] [Full Text]  
  • Vasyutina, E., Lenhard, D. C., Wende, H., Erdmann, B., Epstein, J. A., Birchmeier, C. (2007). RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells. Proc. Natl. Acad. Sci. USA 104: 4443-4448 [Abstract] [Full Text]  
  • Schuster-Gossler, K., Cordes, R., Gossler, A. (2007). Premature myogenic differentiation and depletion of progenitor cells cause severe muscle hypotrophy in Delta1 mutants. Proc. Natl. Acad. Sci. USA 104: 537-542 [Abstract] [Full Text]  
  • Shen, H., McElhinny, A. S., Cao, Y., Gao, P., Liu, J., Bronson, R., Griffin, J. D., Wu, L. (2006). The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis. Genes Dev. 20: 675-688 [Abstract] [Full Text]  
  • Rath, N., Wang, Z., Lu, M. M., Morrisey, E. E. (2005). LMCD1/Dyxin Is a Novel Transcriptional Cofactor That Restricts GATA6 Function by Inhibiting DNA Binding. Mol. Cell. Biol. 25: 8864-8873 [Abstract] [Full Text]  
  • Zhu, B., Ramachandran, B., Gulick, T. (2005). Alternative Pre-mRNA Splicing Governs Expression of a Conserved Acidic Transactivation Domain in Myocyte Enhancer Factor 2 Factors of Striated Muscle and Brain. J. Biol. Chem. 280: 28749-28760 [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]  
  • Kislinger, T., Gramolini, A. O., Pan, Y., Rahman, K., MacLennan, D. H., Emili, A. (2005). Proteome Dynamics during C2C12 Myoblast Differentiation. Mol. Cell. Proteomics 4: 887-901 [Abstract] [Full Text]  
  • Kim, T.-g., Chen, J., Sadoshima, J., Lee, Y. (2004). Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors. Mol. Cell. Biol. 24: 10151-10160 [Abstract] [Full Text]  
  • Wilson-Rawls, J., Rhee, J. M., Rawls, A. (2004). Paraxis Is a Basic Helix-Loop-Helix Protein That Positively Regulates Transcription through Binding to Specific E-box Elements. J. Biol. Chem. 279: 37685-37692 [Abstract] [Full Text]  
  • Delfini, M.-C., Duprez, D. (2004). Ectopic Myf5 or MyoD prevents the neuronal differentiation program in addition to inducing skeletal muscle differentiation, in the chick neural tube. Development 131: 713-723 [Abstract] [Full Text]  
  • Winokur, S. T., Chen, Y.-W., Masny, P. S., Martin, J. H., Ehmsen, J. T., Tapscott, S. J., van der Maarel, S. M., Hayashi, Y., Flanigan, K. M. (2003). Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet 12: 2895-2907 [Abstract] [Full Text]  
  • Yeh, T.-S., Lin, Y.-M., Hsieh, R.-H., Tseng, M.-J. (2003). Association of Transcription Factor YY1 with the High Molecular Weight Notch Complex Suppresses the Transactivation Activity of Notch. J. Biol. Chem. 278: 41963-41969 [Abstract] [Full Text]  
  • Schroeder, T., Fraser, S. T., Ogawa, M., Nishikawa, S., Oka, C., Bornkamm, G. W., Nishikawa, S.-I., Honjo, T., Just, U. (2003). Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis. Proc. Natl. Acad. Sci. USA 100: 4018-4023 [Abstract] [Full Text]  
  • Dorsch, M., Zheng, G., Yowe, D., Rao, P., Wang, Y., Shen, Q., Murphy, C., Xiong, X., Shi, Q., Gutierrez-Ramos, J.-C., Fraser, C., Villeval, J.-L. (2002). Ectopic expression of Delta4 impairs hematopoietic development and leads to lymphoproliferative disease. Blood 100: 2046-2055 [Abstract] [Full Text]  
  • Espinosa, L., Santos, S., Ingles-Esteve, J., Munoz-Canoves, P., Bigas, A. (2002). p65-NF{kappa}B synergizes with Notch to activate transcription by triggering cytoplasmic translocation of the nuclear receptor corepressor N-CoR. J. Cell Sci. 115: 1295-1303 [Abstract] [Full Text]  
  • Jehn, B. M., Dittert, I., Beyer, S., von der Mark, K., Bielke, W. (2002). c-Cbl Binding and Ubiquitin-dependent Lysosomal Degradation of Membrane-associated Notch1. J. Biol. Chem. 277: 8033-8040 [Abstract] [Full Text]  
  • Liu, D., Black, B. L., Derynck, R. (2001). TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 15: 2950-2966 [Abstract] [Full Text]  
  • Wang, J., Shelly, L., Miele, L., Boykins, R., Norcross, M. A., Guan, E. (2001). Human Notch-1 Inhibits NF-{{kappa}}B Activity in the Nucleus Through a Direct Interaction Involving a Novel Domain. J. Immunol. 167: 289-295 [Abstract] [Full Text]  
  • Hirsinger, E, Malapert, P, Dubrulle, J, Delfini, M., Duprez, D, Henrique, D, Ish-Horowicz, D, Pourquie, O (2001). Notch signalling acts in postmitotic avian myogenic cells to control MyoD activation. Development 128: 107-116 [Abstract]  
  • Delfini, M, Hirsinger, E, Pourquie, O, Duprez, D (2000). Delta 1-activated notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis. Development 127: 5213-5224 [Abstract]  
  • Rones, M., McLaughlin, K., Raffin, M, Mercola, M (2000). Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis. Development 127: 3865-3876 [Abstract]  
  • Yamamoto, N., Yamamoto, S.-i., Inagaki, F., Kawaichi, M., Fukamizu, A., Kishi, N., Matsuno, K., Nakamura, K., Weinmaster, G., Okano, H., Nakafuku, M. (2001). Role of Deltex-1 as a Transcriptional Regulator Downstream of the Notch Receptor. J. Biol. Chem. 276: 45031-45040 [Abstract] [Full Text]  
  • Gao, X., Chandra, T., Gratton, M.-O., Quelo, I., Prud'homme, J., Stifani, S., St-Arnaud, R. (2001). HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. JCB 154: 1161-1172 [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»