Functional characterization of mouse fetal TnI gene promoters in myocardial cells

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

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)605-613
Number of pages9
JournalJournal of Biomedical Science
Volume15
Issue number5
DOIs
StatePublished - Sep 1 2008

Keywords

  • Gene regulation
  • Myocardium
  • Myofibril protein
  • Slow skeletal troponin I
  • Thyroid hormone

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Du, J., Nan, C., Huang, J. J., Zhang, C., Liu, J., Jia, P., Abers, M., & Huang, X. P. (2008). Functional characterization of mouse fetal TnI gene promoters in myocardial cells. Journal of Biomedical Science, 15(5), 605-613. https://doi.org/10.1007/s11373-008-9246-y