July 1, 1994Molecular and Cellular Biology
Transcription Factor GATA-4 Regulates Cardiac Muscle-Specific Expression of the α-Myosin Heavy-Chain Gene
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Discussion
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Implication
Experimental study reveals GATA-4 drives alpha-myosin heavy-chain gene expression in myocardial cells, indicating a coordinated mechanism for cardiac phenotype control.
Key Points
- Determine whether the cardiac-restricted transcription factor GATA-4 regulates muscle-specific expression of the alpha-myosin heavy-chain (alpha-MHC) gene.
- Mutated individual and combined GATA-binding sites within the alpha-MHC proximal enhancer to measure transcriptional activity in the adult myocardium.
- Assayed ectopic promoter activation by coinjecting GATA-4 expression vectors into skeletal muscle and fibroblasts, and evaluated GATA-4 DNA binding in cardiomyocytes treated with triiodothyronine or retinoic acid.
- Mutation of single GATA-binding sites decreased promoter activity by 50%, whereas mutating both sites reduced activity by 88% in the adult myocardium.
- Co-injecting GATA-4 enabled ectopic alpha-MHC expression in skeletal muscle cells, and treatment with triiodothyronine or retinoic acid significantly up-regulated GATA-4 DNA binding activity.
Cite This Study
Molkentin et al. (1994) studied this question.