Regulatory Elements Governing Transcription in Specialized Myofiber Subtypes

Zhen Yan, Antonio L. Serrano, Stefano Schiaffino, Rhonda Bassel-Duby, R. Sanders Williams

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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 germline 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.

Original languageEnglish (US)
Pages (from-to)17361-17366
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number20
DOIs
StatePublished - May 18 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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