Identification of cis elements in the cardiac troponin T gene conferring specific expression in cardiac muscle of transgenic mice

Q. Wang, C. D. Sigmund, J. J.C. Lin

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


To investigate the underlying mechanism regulating cardiac gene expression, transgenic mice carrying the rat cardiac troponin T proximal promoter (-497 bp from the transcriptional start site) fused to a LacZ or chloramphenicol acetyltransferase (CAT) reporter gene were analyzed. The LacZ expression pattern throughout development was very similar to that of the endogenous cardiac troponin T gene. Within this promoter, a high degree of sequence homology was found at 2 sites, modules D (-335 to -289 bp) and F (- 249 to -209 bp). Both regions contain at least a TCTG(G/C) direct repeat and an A/T-rich site, whereas only the F module has a muscle enhancer factor 2 (MEF2)-like motif. No significant decrease in CAT transgene expression was observed when only the MEF2 core sequence was mutated. However, when the MEF2 core sequence and its flanking TCTGG site were mutated (Mut5), CAT transgene expression was significantly decreased in the heart, and ectopic expression of the transgene was also observed. When mutations were introduced into this promoter to destroy all upstream TCTG(G/C) direct repeats in the D module (MutD), CAT expression remained cardiac specific, but the expression level was dramatically decreased. Relaxation of cardiac-specific transgene expression became even more severe in transgenic mice carrying double mutations (Mut[D+5]). In addition, CAT activity in the heart was nearly abolished. These results suggest that D and F modules have an additive function in determining the level of expression in the heart and only the F module confers cardiac-specific expression.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalCirculation research
Issue number4
StatePublished - Mar 3 2000
Externally publishedYes


  • A/T-rich region
  • Cardiac-specific gene expression
  • Promoter
  • TCTG(G/C) direct repeat
  • Transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Identification of cis elements in the cardiac troponin T gene conferring specific expression in cardiac muscle of transgenic mice'. Together they form a unique fingerprint.

Cite this