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Functional characterization of mouse fetal TnI gene promoters in myocardial cells

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (∼1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Analysis of the sequence revealed several putative regulatory domains and binding sites (Sp1 binding sites, GATA binding site, MyoD, CREB, MEF2, AP1, NFκB, etc). Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. An inhibitory domain was revealed within the sequence between −1,700 to −1,780. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells whereas this effect was not evident in CHO cells.

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Acknowledgements

This work was supported by grants from NIH (1S06GM073621) and American Heart Association Florida/Puerto Rico Affiliate and from the Center of Excellence for Biomedical and Marine Biotechnology at Florida Atlantic University (X-P.H). J.D is a recipient of Pre-doctoral Fellowship Award from AHA/Puerto Rico Affiliate.

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Authors and Affiliations

  1. Department of Biomedical Science, Center for Molecular Biology and Biotechnology, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA

    J. Du, C. Nan, J. J. Huang, C. Zhang, J. Liu, P. Jia, M. Abers & X. P. Huang

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  1. J. Du
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  2. C. Nan
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  3. J. J. Huang
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  4. C. Zhang
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  5. J. Liu
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  6. P. Jia
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  7. M. Abers
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  8. X. P. Huang
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Correspondence to X. P. Huang.

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Du, J., Nan, C., Huang, J.J. et al. Functional characterization of mouse fetal TnI gene promoters in myocardial cells. J Biomed Sci 15, 605–613 (2008). https://doi.org/10.1007/s11373-008-9246-y

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  • DOI: https://doi.org/10.1007/s11373-008-9246-y

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