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

57 Citations (Scopus)

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 - Jun 5 1992

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Helix-Loop-Helix Motifs
Myogenin
Transforming Growth Factors
Transcription
Muscle
Muscles
DNA sequences
Proteins
MyoD Protein
Genes
E-Box Elements
Muscle Proteins
Reporter Genes
Oligomers
Transcriptional Activation
Chemical activation
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Repression of myogenin function by TGF-β1 is targeted at the basic helix-loop-helix motif and is independent of E2A products. / Martin, James F.; Li, Li; Olson, Eric N.

In: Journal of Biological Chemistry, Vol. 267, No. 16, 05.06.1992, p. 10956-10960.

Research output: Contribution to journalArticle

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