The GATA-4 transcription factor transactivates the cardiac-specific troponin C promoter-enhancer in non-muscle cells.
The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Here, we demonstrate that the slow/cardiac-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted, zinc finger transcription factor, GATA-4 and that GATA-4 mRNA and protein is expressed in cardiac myocytes. In addition, GATA-4 binding sites were identified in several previously characterized cardiac-specific transcriptional regulatory elements. The cTnC GATA-4 binding site is required for transcriptional enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by over-expression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.
Department of Medicine, University of Chicago, IL, USA.
H S
HS
Ip
D B
DB
Wilson
M
M
Heikinheimo
J M
JM
Leiden
M S
MS
Parmacek
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050991:GATA4 Transcription Factor; D018014:Gene Transfer Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014336:Troponin / Q000235:genetics* / Q000378:metabolism; D019209:Troponin C
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D014157:Transcription Factors; D014336:Troponin; D019209:Troponin C