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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,
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.
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.
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