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 language | English (US) |
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Pages (from-to) | 10956-10960 |
Number of pages | 5 |
Journal | Journal of Biological Chemistry |
Volume | 267 |
Issue number | 16 |
State | Published - 1992 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology