Browse > Article

Inhibition of DNA Methylation Is Involved in Transdifferentiation of Myoblasts into Smooth Muscle Cells  

Lee, Won Jun (College of Health Science, Ewha Womans University)
Kim, Hye Jin (College of Health Science, Ewha Womans University)
Abstract
Despite the importance of cell fate decisions regulated by epigenetic programming, no experimental model has been available to study transdifferentiation from myoblasts to smooth muscle cells. In the present study, we show that myoblast cells can be induced to transdifferentiate into smooth muscle cells by modulating their epigenetic programming. The DNA methylation inhibitor, zubularine, induced the morphological transformation of C2C12 myoblasts into smooth muscle cells accompanied by de novo synthesis of smooth muscle markers such as smooth muscle ${\alpha}$-actin and transgelin. Furthermore, an increase of p21 and decrease of cyclinD1 mRNA were observed following zebularine treatment, pointing to inhibition of cell cycle progression. This system may provide a useful model for studying the early stages of smooth muscle cell differentiation.
Keywords
Differentiation; DNA Methylation; Smooth Muscle; Zebularine;
Citations & Related Records

Times Cited By Web Of Science : 5  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Owens, G. K. (1995) Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 75, 487−517
2 Urnov, F. D. (2003) Chromatin remodeling as a guide to transcriptional regulatory networks in mammals. J. Cell Biochem. 88, 684−694
3 Manabe, I. and Owens, I. M. (2001) Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel p19-derived in vitro smooth muscle differentiation. Circ. Res. 88, 1127−1134
4 Raff, M. (2003) Adult stem cell plasticity: fact or artifact? Annu. Rev. Cell Dev. Biol. 19, 1−22
5 Berger, S. L. (2007) The complex language of chromatin regulation during transcription. Nature 447, 407−412
6 Kohyama, J., Abe, H., Shimazaki, T., Koizumi, A., Nakashima, K., et al. (2001) Brain from bone: efficient 'meta-differentiation' of marrow stroma-derived mature osteoblasts to neurons with noggin or a demethylating agent. Differentiation 68, 235−244
7 Jones, P. A. and Taylor, S. M. (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20, 85−93
8 Kondo, T. (2006) Epigenetic alchemy for cell fate conversion. Curr. Opin. Genet. Dev. 16, 502−507
9 Bird, A. P. and Wolffe, A. P. (1999) Methylation-induced repression-- belts, braces, and chromatin. Cell 99, 451−454
10 Cheng, J. C., Matsen, C. B., Gonzales, F. A., Ye, W., Greer, S., et al. (2003) Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J. Natl. Cancer Inst. 95, 399−409
11 Woodbury, D., Reynolds, K., and Black, I. B. (2002) Adult bone marrow stromal stem cells express germline, ectodermal, and mesodermal genes prior to neurogenesis. J. Neurosci. Res. 69, 908−917
12 Bestor, T. H., Laudano, A., Mattaliano, R., and Ingram, V. (1988) Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J. Mol. Biol. 203, 971−983