QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online October 12, 2006
doi: 10.1242/10.1242/jcs.03185

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karamboulas, C. Articles by Skerjanc, I. S. Search for Related Content PubMed PubMed Citation Articles by Karamboulas, C. Articles by Skerjanc, I. S. Social Bookmarking                         What's this?

HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage

¹ Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario, N6A 5C1, Canada
² Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada

^* Author for correspondence (e-mail: iskerjan{at}uottawa.ca)

Accepted 25 July 2006

Class II histone deacetylases (HDAC4, HDAC5, HDAC7 and HDAC9) have been shown to interact with myocyte enhancer factors 2 (MEF2s) and play an important role in the repression of cardiac hypertrophy. We examined the role of HDACs during the differentiation of P19 embryonic carcinoma stem cells into cardiomyoctyes. Treatment of aggregated P19 cells with the HDAC inhibitor trichostatin A induced the entry of mesodermal cells into the cardiac muscle lineage, shown by the upregulation of transcripts Nkx2-5, MEF2C, GATA4 and cardiac -actin. Furthermore, the overexpression of HDAC4 inhibited cardiomyogenesis, shown by the downregulation of cardiac muscle gene expression. Class II HDAC activity is inhibited through phosphorylation by Ca²⁺/calmodulin-dependent kinase (CaMK). Expression of an activated CaMKIV in P19 cells upregulated the expression of Nkx2-5, GATA4 and MEF2C, enhanced cardiac muscle development, and activated a MEF2-responsive promoter. Moreover, inhibition of CaMK signaling downregulated GATA4 expression. Finally, P19 cells constitutively expressing a dominant-negative form of MEF2C, capable of binding class II HDACs, underwent cardiomyogenesis more efficiently than control cells, implying the relief of an inhibitor. Our results suggest that HDAC activity regulates the specification of mesoderm cells into cardiomyoblasts by inhibiting the expression of GATA4 and Nkx2-5 in a stem cell model system.

Key words: Cardiomyogenesis, Gene expression, Stem cells

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Margariti, Q. Xiao, A. Zampetaki, Z. Zhang, H. Li, D. Martin, Y. Hu, L. Zeng, and Q. Xu Splicing of HDAC7 modulates the SRF-myocardin complex during stem-cell differentiation towards smooth muscle cells J. Cell Sci., February 15, 2009; 122(4): 460 - 470. [Abstract] [Full Text] [PDF]

				T. Thum, D. Catalucci, and J. Bauersachs MicroRNAs: novel regulators in cardiac development and disease Cardiovasc Res, September 1, 2008; 79(4): 562 - 570. [Abstract] [Full Text] [PDF]

				D. E. Frigo and D. P. McDonnell Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation Mol. Cancer Ther., March 1, 2008; 7(3): 659 - 669. [Abstract] [Full Text] [PDF]

				C. Karamboulas, G. D. Dakubo, J. Liu, Y. De Repentigny, K. Yutzey, V. A. Wallace, R. Kothary, and I. S. Skerjanc Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis J. Cell Sci., October 15, 2006; 119(20): 4315 - 4321. [Abstract] [Full Text] [PDF]