Repression of myogenin function by TGF-β1 is targeted at the basic helix- loop-helix motif and is independent of E2A products

James F. Martin, Li Li, Eric N. Olson

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The muscle-specific helix-loop-helix (HLH) proteins myogenin, MyoD, myf5, and MRF4 form hetero-oligomers with ubiquitous HLH proteins encoded by the E2A gene and activate muscle transcription by binding to a DNA sequence known as an E-box (CANNTG). Transforming growth factor-β (TGF-β) can inhibit muscle differentiation by silencing the transcription-activating potential of myogenic HLH proteins without affecting their ability to bind DNA. We show that repression by TGF-β is directed at the basic-HLH motif of myogenin and is independent of E2A products. Using a series of reporter genes as targets for trans-activation by myogenin, transcriptional repression by TGF-β is also shown to map to the E-box motif and to not require heterologous DNA sequence elements. These results demonstrate that TGF-β represses muscle- specific transcription through a post-translational mechanism that renders the basic-HLH regions of the myogenic regulators nonfunctional. The selective repression of myogenic HLH proteins by TGF-β indicates that the TGF-β signaling system can discriminate between different classes of HLH proteins and implies that myogenic HLH proteins activate muscle-specific transcription through a unique mechanism.

Original languageEnglish (US)
Pages (from-to)10956-10960
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number16
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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