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Molecular and Cellular Biology, April 2001, p. 2404-2412, Vol. 21, No. 7
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.7.2404-2412.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Molecular Distinction between Specification and Differentiation in the Myogenic Basic Helix-Loop-Helix Transcription Factor Family

Donald A. Bergstrom1,2 and Stephen J. Tapscott1,2,3,*

Program in Developmental Biology, Division of Human Biology, Fred Hutchinson Cancer Research Center,1 and Departments of Pathology2 and Neurology,3 University of Washington School of Medicine, Seattle, Washington

Received 11 October 2000/Returned for modification 1 December 2000/Accepted 11 January 2001

The myogenic basic helix-loop-helix (bHLH) proteins regulate both skeletal muscle specification and differentiation: MyoD and Myf5 establish the muscle lineage, whereas myogenin mediates differentiation. Previously, we demonstrated that MyoD was more efficient than myogenin at initiating the expression of skeletal muscle genes, and in this study we present the molecular basis for this difference. A conserved amphipathic alpha-helix in the carboxy terminus of the myogenic bHLH proteins has distinct activities in MyoD and myogenin: the MyoD helix facilitates the initiation of endogenous gene expression, whereas the myogenin helix functions as a general transcriptional activation domain. Thus, the alternate use of a similar motif for gene initiation and activation provides a molecular basis for the distinction between specification and differentiation within the myogenic bHLH gene family.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, Room C3-168, 1100 Fairview Ave. N., Seattle, WA 98108-1024. Phone: (206) 667-4499. Fax: (206) 667-6524. E-mail: stapscot{at}fhcrc.org.

Molecular and Cellular Biology, April 2001, p. 2404-2412, Vol. 21, No. 7
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.7.2404-2412.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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