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 Ueyama, T.
Right arrow Articles by Izumo, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ueyama, T.
Right arrow Articles by Izumo, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 9222-9232, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.9222-9232.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Myocardin Expression Is Regulated by Nkx2.5, and Its Function Is Required for Cardiomyogenesis

Tomomi Ueyama, Hideko Kasahara,{dagger} Takahiro Ishiwata, Qing Nie, and Seigo Izumo*

Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215

Received 14 March 2003/ Returned for modification 5 May 2003/ Accepted 21 July 2003

Nkx2.5 (also known as Csx) is an evolutionarily conserved cardiac transcription factor of the homeobox gene family. Nkx2.5 is required for early heart development, since Nkx2.5-null mice die before completion of cardiac looping. To identify genes regulated by Nkx2.5 in the developing heart, we performed subtractive hybridization by using RNA isolated from wild-type and Nkx2.5-null hearts at embryonic day 8.5. We isolated a mouse cDNA encoding myocardin A, which is an alternative spliced isoform of myocardin and the most abundant isoform in the heart from embryo to adult. The expression of myocardin A and myocardin was markedly downregulated in Nkx2.5-null mouse hearts. Transient-cotransfection analysis showed that Nkx2.5 transactivates the myocardin promoter. Inhibition of myocardin function in the teratocarcinoma cell line P19CL6 prevented differentiation into cardiac myocytes after dimethyl sulfoxide treatment. Myocardin A transactivated the promoter of the atrial natriuretic factor gene through the serum response element, which was augmented by bone morphogenetic protein 2 and transforming growth factor ß-activated kinase 1. These results suggest that myocardin expression is regulated by Nkx2.5 and that its function is required for cardiomyogenesis.

* Corresponding author. Mailing address: Cardiovascular Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215. Phone: (617) 667-4858. Fax: (617) 975-5268. E-mail: sizumo{at}caregroup.harvard.edu.

{dagger} Present address: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610-0274.

Molecular and Cellular Biology, December 2003, p. 9222-9232, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.9222-9232.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Davis, B. N., Hilyard, A. C., Nguyen, P. H., Lagna, G., Hata, A. (2009). Induction of MicroRNA-221 by Platelet-derived Growth Factor Signaling Is Critical for Modulation of Vascular Smooth Muscle Phenotype. J. Biol. Chem. 284: 3728-3738 [Abstract] [Full Text]  
  • Ferdous, A., Caprioli, A., Iacovino, M., Martin, C. M., Morris, J., Richardson, J. A., Latif, S., Hammer, R. E., Harvey, R. P., Olson, E. N., Kyba, M., Garry, D. J. (2009). Nkx2-5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo. Proc. Natl. Acad. Sci. USA 106: 814-819 [Abstract] [Full Text]  
  • Tagawa, M., Ueyama, T., Ogata, T., Takehara, N., Nakajima, N., Isodono, K., Asada, S., Takahashi, T., Matsubara, H., Oh, H. (2008). MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis. Am. J. Physiol. Cell Physiol. 295: C490-C498 [Abstract] [Full Text]  
  • Byon, C. H., Javed, A., Dai, Q., Kappes, J. C., Clemens, T. L., Darley-Usmar, V. M., McDonald, J. M., Chen, Y. (2008). Oxidative Stress Induces Vascular Calcification through Modulation of the Osteogenic Transcription Factor Runx2 by AKT Signaling. J. Biol. Chem. 283: 15319-15327 [Abstract] [Full Text]  
  • Ogata, T., Ueyama, T., Isodono, K., Tagawa, M., Takehara, N., Kawashima, T., Harada, K., Takahashi, T., Shioi, T., Matsubara, H., Oh, H. (2008). MURC, a Muscle-Restricted Coiled-Coil Protein That Modulates the Rho/ROCK Pathway, Induces Cardiac Dysfunction and Conduction Disturbance. Mol. Cell. Biol. 28: 3424-3436 [Abstract] [Full Text]  
  • Kolodziejska, K. M., Noyan-Ashraf, M.H., Nagy, A., Bacon, A., Frampton, J., Xin, H.-B., Kotlikoff, M. I., Husain, M. (2008). c-Myb-Dependent Smooth Muscle Cell Differentiation. Circ. Res. 102: 554-561 [Abstract] [Full Text]  
  • Wang, J., Li, A., Wang, Z., Feng, X., Olson, E. N., Schwartz, R. J. (2007). Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts. Mol. Cell. Biol. 27: 622-632 [Abstract] [Full Text]  
  • Creemers, E. E., Sutherland, L. B., McAnally, J., Richardson, J. A., Olson, E. N. (2006). Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development. Development 133: 4245-4256 [Abstract] [Full Text]  
  • Doi, H., Iso, T., Sato, H., Yamazaki, M., Matsui, H., Tanaka, T., Manabe, I., Arai, M., Nagai, R., Kurabayashi, M. (2006). Jagged1-selective Notch Signaling Induces Smooth Muscle Differentiation via a RBP-J{kappa}-dependent Pathway. J. Biol. Chem. 281: 28555-28564 [Abstract] [Full Text]  
  • Elliott, D. A., Solloway, M. J., Wise, N., Biben, C., Costa, M. W., Furtado, M. B., Lange, M., Dunwoodie, S., Harvey, R. P. (2006). A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery. Development 133: 1311-1322 [Abstract] [Full Text]  
  • Callis, T. E., Cao, D., Wang, D.-Z. (2005). Bone Morphogenetic Protein Signaling Modulates Myocardin Transactivation of Cardiac Genes. Circ. Res. 97: 992-1000 [Abstract] [Full Text]  
  • van Tuyn, J., Knaan-Shanzer, S., van de Watering, M. J.M., de Graaf, M., van der Laarse, A., Schalij, M. J., van der Wall, E. E., de Vries, A. A.F., Atsma, D. E. (2005). Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin. Cardiovasc Res 67: 245-255 [Abstract] [Full Text]  
  • Youn, H., Koo, Y., Ji, I., Ji, T. H. (2005). An Upstream Initiator-Like Element Suppresses Transcription of the Rat Luteinizing Hormone Receptor Gene. Mol. Endocrinol. 19: 1318-1328 [Abstract] [Full Text]  
  • Small, E. M., Warkman, A. S., Wang, D.-Z., Sutherland, L. B., Olson, E. N., Krieg, P. A. (2005). Myocardin is sufficient and necessary for cardiac gene expression in Xenopus. Development 132: 987-997 [Abstract] [Full Text]  
  • Oh, J., Wang, Z., Wang, D.-Z., Lien, C.-L., Xing, W., Olson, E. N. (2004). Target Gene-Specific Modulation of Myocardin Activity by GATA Transcription Factors. Mol. Cell. Biol. 24: 8519-8528 [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»