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Chromatin Immunoprecipitation Assay for Tissue-specific Genes using Early-stage Mouse Embryos
Published on: April 29, 2011
Control of myogenic differentiation by cellular oncogenes
1Department of Medicine, Baylor College of Medicine, Methodist Hospital, Houston, TX 77030.
Molecular Neurobiology
|January 1, 1988
Summary
Cellular oncogenes like src and ras inhibit muscle cell differentiation by blocking tissue-specific gene expression, independent of DNA synthesis. Down-regulation of c-myc is not required for myogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Skeletal muscle differentiation (myogenesis) requires cell cycle exit and cessation of DNA synthesis.
- Growth factors and serum components inhibit myogenesis via unknown intracellular pathways.
- Cellular proto-oncogenes are known to mediate growth factor signaling for cell proliferation.
Purpose of the Study:
- To investigate the role of cellular oncogenes in regulating tissue-specific gene expression during muscle cell development.
- To test the hypothesis that oncogenes can regulate, rather than just promote proliferation, in differentiating myoblasts.
- To elucidate the signaling mechanisms by which oncogenes impact myogenesis.
Main Methods:
- Genetic modification of myoblasts with viral oncogenes, cellular homologs, and inducible chimeric oncogenes.
- Analysis of endogenous cellular oncogene regulation during myogenesis.
- Assessment of effects on cell cycle status, DNA synthesis, and expression of muscle-specific genes.
Main Results:
- Down-regulation of c-myc is not essential for myogenesis; its inhibitory effects on differentiation depend on sustained proliferation.
- Activated src and ras genes directly block myocyte differentiation through a mechanism independent of DNA synthesis.
- These inhibitory effects are rapidly reversible and mimic those of inhibitory growth factors.
Conclusions:
- Cellular oncogenes, particularly activated src and ras, can directly inhibit muscle differentiation.
- The mechanism involves a pathway independent of DNA synthesis, suggesting regulation of tissue-specific gene expression.
- Transforming growth factor-beta and ras proteins may share a common transacting transcriptional signal to inhibit diverse muscle-specific genes.
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