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J. Biol. Chem., Vol. 276, Issue 20, 17361-17366, May 18, 2001
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From the 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.
Regulatory Elements Governing Transcription in Specialized
Myofiber Subtypes*
,, and¶
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
*
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.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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