Key result
Mutation or deletion of GATA elements induced a strong transcriptional activation of the cTnI promoter in regenerating skeletal muscle and cultured skeletal muscle cells.
The cardiac troponin I gene promoter is repressed in skeletal muscle cells by GATA-like factors, preventing its expression outside of cardiac tissue.
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GATA repression may enforce cardiac cTnI specificity; leaves open therapeutic targeting in human gene therapy or regeneration.
BACKGROUND: We reported previously that the cardiac troponin I (cTnI) promoter drives cardiac-specific expression of reporter genes in cardiac muscle cells and in transgenic mice, and that disruption of GATA elements inactivates the cTnI promoter in cultured cardiomyocytes. We have now examined the role of cTnI promoter GATA elements in skeletal muscle cells. RESULTS: Mutation or deletion of GATA elements induces a strong transcriptional activation of the cTnI promoter in regenerating skeletal muscle and in cultured skeletal muscle cells. Electrophoretic mobility shift assays show that proteins present in nuclear extracts of C2C12 muscle cells bind the GATA motifs present in the cTnI promoter. However, GATA protein complex formation is neither reduced nor supershifted by antibodies specific for GATA-2, -3 and -4, the only GATA transcripts present in muscle cells. CONCLUSION: These findings indicate that the cTnI gene promoter is repressed in skeletal muscle cells by GATA-like factors and open the way to further studies aimed at identifying these factors.
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Lisi et al. (2007) studied this question. Mutation or deletion of GATA elements in cTnI promoter vs. Wild-type cTnI promoter was evaluated on cTnI promoter activity (CAT activity) (up to 15-fold increase). Mutation or deletion of GATA elements induced a strong transcriptional activation of the cTnI promoter in regenerating skeletal muscle and cultured skeletal muscle cells.
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