Hedgehog Signaling Regulates MyoD Expression and Activity*
| العنوان: | Hedgehog Signaling Regulates MyoD Expression and Activity* |
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| المؤلفون: | Valerie A. Wallace, Joel V. Fair, Grace Li, Ilona S. Skerjanc, Neven Bosiljcic, Ashraf Al Madhoun, Erin S. Coyne, Anastassia Voronova, Catherine St-Louis, Sherry Thurig, Nadine Wiper-Bergeron |
| المصدر: | The Journal of Biological Chemistry |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Pluripotent Stem Cells, animal structures, Skeletal Muscle, Satellite Cells, Skeletal Muscle, Kruppel-Like Transcription Factors, Gene Expression, Mice, Transgenic, Biology, Development, Zinc Finger Protein Gli2, MyoD, Muscle Development, Biochemistry, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, MyoD Protein, Embryonic Stem Cell, Animals, Gene Regulation, Hedgehog Proteins, Molecular Biology, Myogenin, 030304 developmental biology, 0303 health sciences, PITX2, Myogenesis, MEF2 Transcription Factors, Cell Biology, musculoskeletal system, Hedgehog signaling pathway, P19 cell, Gene Expression Regulation, Myogenic Regulatory Factors, Multiprotein Complexes, Myogenic regulatory factors, Cancer research, Hedgehog Signaling, MEF2, tissues, Transcription, 030217 neurology & neurosurgery, Gli, Signal Transduction |
| الوصف: | Background: Hedgehog (Hh) signaling regulates skeletal myogenesis; however, the molecular mechanisms involved are not fully understood. Results: Gli2, a transactivator of Hh signaling, associates with MyoD gene elements, regulating MyoD expression, and binds to MyoD protein, regulating its ability to induce myogenesis. Conclusion: Hh signaling is linked to MyoD gene expression and MyoD protein function. Significance: Novel mechanistic insight is gained into the Hh-regulated myogenesis. The inhibition of MyoD expression is important for obtaining muscle progenitors that can replenish the satellite cell niche during muscle repair. Progenitors could be derived from either embryonic stem cells or satellite cells. Hedgehog (Hh) signaling is important for MyoD expression during embryogenesis and adult muscle regeneration. To date, the mechanistic understanding of MyoD regulation by Hh signaling is unclear. Here, we demonstrate that the Hh effector, Gli2, regulates MyoD expression and associates with MyoD gene elements. Gain- and loss-of-function experiments in pluripotent P19 cells show that Gli2 activity is sufficient and required for efficient MyoD expression during skeletal myogenesis. Inhibition of Hh signaling reduces MyoD expression during satellite cell activation in vitro. In addition to regulating MyoD expression, Hh signaling regulates MyoD transcriptional activity, and MyoD activates Hh signaling in myogenic conversion assays. Finally, Gli2, MyoD, and MEF2C form a protein complex, which enhances MyoD activity on skeletal muscle-related promoters. We therefore link Hh signaling to the function and expression of MyoD protein during myogenesis in stem cells. |
| اللغة: | English |
| تدمد: | 1083-351X 0021-9258 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fda1f770583fc2306b5c224c4582f876Test http://europepmc.org/articles/PMC3567689Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fda1f770583fc2306b5c224c4582f876 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
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