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Originally published In Press as doi:10.1074/jbc.M101251200 on February 26, 2001

J. Biol. Chem., Vol. 276, Issue 20, 17361-17366, May 18, 2001
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Regulatory Elements Governing Transcription in Specialized Myofiber Subtypes*

Zhen YanDagger , Antonio L. Serrano§, Stefano Schiaffino§, Rhonda Bassel-DubyDagger , and R. Sanders WilliamsDagger

From the Dagger  Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and the § Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche Center for Muscle Biology and Physiopathology, University of Padova, 35121 Padova, Italy

Skeletal myofibers of vertebrates acquire specialized metabolic and physiological properties as a consequence of developmental cues in the embryo and different patterns of contractile activity in the adult. The myoglobin gene is regulated stringently in muscle fibers, such that high myoglobin expression is observed in mitochondria-rich, oxidative myofibers (Types I and IIa) compared with glycolytic fibers (Type IIb). Using germ-line transgenesis and somatic cell gene transfer methods, we defined discrete regions of the murine and human genes encoding myoglobin that are sufficient to confer muscle- and fiber type-specific expression to reporter genes. Mutational analysis confirms the importance of A/T-rich, MEF2-binding motifs in myoglobin gene regulation, as suggested by previous studies using different experimental approaches. In addition, we demonstrated a previously unsuspected role for an intragenic E-box motif as a negative regulatory element contributing to the tightly regulated variation in myoglobin gene expression among particular myofiber subtypes.

* This work was supported by grants from the National Institutes of Health, the American Heart Association (grant-in-aid to Z. Y.), and the Donald W. Reynolds Cardiovascular Clinical Research Center, Dallas, TX.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.

To whom correspondence should be addressed: University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., NB11.200, Dallas, TX 75390-8573; Tel.: 214-648-1400; Fax: 214-648-450; E-mail: williams@ryburn.swmed.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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