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Molecular and Cellular Biology, April 2001, p. 2404-2412, Vol. 21, No. 7
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.
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
*
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.
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