Regulatory elements governing transcription in specialized myofiber subtypes.
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.
Duke Scholars
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- Transcription, Genetic
- TATA Box
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Proteins
- Promoter Regions, Genetic
- Organ Specificity
- Myoglobin
- Myocardium
- Mutagenesis, Site-Directed
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- TATA Box
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Proteins
- Promoter Regions, Genetic
- Organ Specificity
- Myoglobin
- Myocardium
- Mutagenesis, Site-Directed