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Highly Coordinated Gene Regulation in Mouse Skeletal Muscle Regeneration

Yan, Zhen and Choi, Sangdun and Liu, Xuebin and Zhang, Mei and Schageman, Jeoffrey J. and Lee, Sun Young and Hart, Rebecca and Lin, Ling and Thurmond, Frederick A. and Williams, R. Sanders (2003) Highly Coordinated Gene Regulation in Mouse Skeletal Muscle Regeneration. Journal of Biological Chemistry, 278 (10). pp. 8826-8836. ISSN 0021-9258. doi:10.1074/jbc.M209879200.

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Mammalian skeletal muscles are capable of regeneration after injury. Quiescent satellite cells are activated to reenter the cell cycle and to differentiate for repair, recapitulating features of myogenesis during embryonic development. To understand better the molecular mechanism involved in this process in vivo, we employed high density cDNA microarrays for gene expression profiling in mouse tibialis anterior muscles after a cardiotoxin injection. Among 16,267 gene elements surveyed, 3,532 elements showed at least a 2.5-fold change at one or more time points during a 14-day time course. Hierarchical cluster analysis and semiquantitative reverse transcription-PCR showed induction of genes important for cell cycle control and DNA replication during the early phase of muscle regeneration. Subsequently, genes for myogenic regulatory factors, a group of imprinted genes and genes with functions to inhibit cell cycle progression and promote myogenic differentiation, were induced when myogenic stem cells started to differentiate. Induction of a majority of these genes, including E2f1 and E2f2, was abolished in muscles lacking satellite cell activity after gamma radiation. Regeneration was severely compromised in E2f1 null mice but not affected in E2f2 null mice. This study identifies novel genes potentially important for muscle regeneration and reveals highly coordinated myogenic cell proliferation and differentiation programs in adult skeletal muscle regeneration in vivo.

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Additional Information:© 2003 The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, September 26, 2002, and in revised form, December 2, 2002. Originally published In Press as doi:10.1074/jbc.M209879200 on December 10, 2002. We thank E. N. Olson, R. Bassel-Duby, and B. Annex for comments; J. R. Nevins for providing E2f2 null mice; and A. Pippen, R. E. Rempel, J. M. Shelton, S. C. Williams, C. Pomajzl, and J. M. Stark for excellent technical support. This work was supported by American Heart Association Grant 0130261N (to Z. Y.) and National Institutes of Health Grant AR40849 (to R. S. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The on-line version of this article (available at contains the self-organization map and functional groups.
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American Heart Association0130261N
Issue or Number:10
Record Number:CaltechAUTHORS:YANjbc03a
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5482
Deposited By: Archive Administrator
Deposited On:19 Oct 2006
Last Modified:08 Nov 2021 20:26

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