Transforming growth factor beta represses the actions of myogenin through a mechanism independent of DNA binding.
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 10T1/2 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 beta (TGF-beta) or high serum. Although the final effect of TGF-beta and high serum--inhibition of myogenesis--was the same, their effects on the DNA-binding properties of myogenin in vitro differed. TGF-beta 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-beta. 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-beta acts through a mechanism distal to DNA sequence recognition by myogenin and independent of Id.
Brennan
T J
TJ
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Edmondson
D G
DG
Li
L
L
Olson
E N
EN
D000818:Animals; D002451:Cell Compartmentation; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009132:Muscles / Q000166:cytology*; D018008:Myogenin; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D009124:Muscle Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D003402:Creatine Kinase