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Molecular and Cellular Biology, September 2002, p. 6199-6208, Vol. 22, No. 17
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.17.6199-6208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells

Jeffrey C. Wyzykowski, Therry I. Winata, Natalia Mitin, Elizabeth J. Taparowsky, and Stephen F. Konieczny*

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392

Received 17 January 2002/ Returned for modification 26 March 2002/ Accepted 4 June 2002

A major control point for skeletal myogenesis revolves around the muscle basic helix-loop-helix gene family that includes MyoD, Myf-5, myogenin, and MRF4. Myogenin and MRF4 are thought to be essential to terminal differentiation events, whereas MyoD and Myf-5 are critical to establishing the myogenic cell lineage and producing committed, undifferentiated myogenic stem cells (myoblasts). Although mouse genetic studies have revealed the importance of MyoD and Myf-5 for myoblast development, the genetic targets of MyoD and Myf-5 activity in undifferentiated myoblasts remain unknown. In this study, we investigated the function of MyoD as a transcriptional activator in undifferentiated myoblasts. By using conditional expression of MyoD, in conjunction with suppression subtractive hybridizations, we show that the Id3 and NP1 (neuronal pentraxin 1) genes become transcriptionally active following MyoD induction in undifferentiated myoblasts. Activation of Id3 and NP1 represents a stable, heritable event that does not rely on continued MyoD activity and is not subject to negative regulation by an activated H-Ras G12V protein. These results are the first to demonstrate that MyoD functions as a transcriptional activator in myogenic stem cells and that this key myogenic regulatory factor exhibits different gene target specificities, depending upon the cellular environment.

* Corresponding author. Mailing address: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392. Phone: (765) 494-7976. Fax: (765) 496-2536. E-mail: sfk{at}bilbo.bio.purdue.edu.

Molecular and Cellular Biology, September 2002, p. 6199-6208, Vol. 22, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.17.6199-6208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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