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PMID:8999959
| Citation |
Chen, B and Lim, RW (1997) Physical and functional interactions between the transcriptional inhibitors Id3 and ITF-2b. Evidence toward a novel mechanism regulating muscle-specific gene expression. J. Biol. Chem. 272:2459-63 |
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| Abstract |
We have used an interaction cloning strategy to identify an inhibitory isoform of the ITF-2 transcription factor, ITF-2b, that interacts with the transcriptional inhibitor Id3/HLH462. The interaction was confirmed in vitro, and inside intact myogenic C2C12 cells. As expected, overexpression of either Id3/HLH462 or ITF-2b effectively inhibited the activation of the muscle-specific creatine kinase promoter by the myogenic transcription factor MyoD. However, when overexpressed simultaneously, ITF-2b and Id3/HLH462 counteracted each other's inhibitory effect to produce a reduced overall inhibition. Moreover, while ITF-2b inhibited the creatine kinase promoter, it acted as a weak transactivator on an artificial promoter consisting of three tandem copies of the consensus myogenic factor DNA binding site. Further investigation indicated that the ITF-2b/MyoD heterodimer bound to its specific DNA binding site in vitro, and the DNA binding was effectively blocked by Id3/HLH462. Additional analysis revealed the presence of transcripts for both the activating (ITF-2a) and inhibitory (ITF-2b) isoforms in differentiating C2C12 cultures, suggesting that both isoforms might participate in regulating the differentiation process. Taken together, this study reveals a more complex pattern of regulatory interactions involving the helix-loop-helix proteins than was previously anticipated. |
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| Keywords |
Actins/genetics; Actins/metabolism; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cells, Cultured; DNA, Complementary/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation; Helix-Loop-Helix Motifs; Inhibitor of Differentiation Proteins; Mice; Muscles/metabolism; Myogenin/genetics; Myogenin/metabolism; Neoplasm Proteins; Nerve Tissue Proteins; Polymerase Chain Reaction; TCF Transcription Factors; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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