Transforming growth factor β represses the actions of myogenin through a mechanism independent of DNA binding

Thomas J. Brennan, Diane G. Edmondson, Li Li, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Myogenin belongs to a family of regulatory factors that can activate myogenesis when transfected into nonmyogenic cells. A conserved DNA sequence, known as an E box, serves as the target for binding and trans-activation by myogenin. Using 10T 1/2 fibroblasts that constitutively express a transfected myogenin cDNA, we show that myogenin accumulates in the nucleus but is unable to initiate myogenesis when cells are maintained with transforming growth factor β (TGF-β) or high serum. Although the final effect of TGF-β and high serum-inhibition of myogenesis-was the same, their effects on the DNA-binding properties of myogenin in vitro differed. TGF-β did not affect the ability of myogenin to bind DNA, whereas serum diminished the in vitro DNA-binding activity of myogenin. The helix-loop-helix (HLH) protein Id, postulated to inhibit DNA binding of other HLH proteins, was induced by high serum but not by TGF-β. The presence of Id correlated with the failure of myogenin to bind the muscle creatine kinase enhancer in vitro. These findings suggest that serum can inhibit myogenesis by attenuating the DNA-binding activity of myogenin, possibly as a consequence of Id protein expression, whereas TGF-β acts through a mechanism distal to DNA sequence recognition by myogenin and independent of Id.

Original languageEnglish (US)
Pages (from-to)3822-3826
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number9
DOIs
StatePublished - 1991

Keywords

  • Id
  • myogenesis

ASJC Scopus subject areas

  • General

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