GATA-4 and MEF2C transcription factors control the tissue-specific expression of the alphaT-catenin gene CTNNA3.

AlphaT-catenin is a recently identified member of the alpha-catenin family of cell-cell adhesion molecules. Its expression is restricted mainly to cardiomyocytes, although it is also expressed in skeletal muscle, testis and brain. Like other alpha-catenins, alphaT-catenin provides an indispensable link between a cadherin-based adhesion complex and the actin cytoskeleton, resulting in strong cell-cell adhesion. We show here that the tissue-specificity of alphaT-catenin expression is controlled by its promoter region. By in silico analysis, we found that the alphaT-catenin promoter contains several binding sites for cardiac and muscle-specific transcription factors. By co-transfection studies in P19 embryonal carcinoma cells, we demonstrated that MEF2C and GATA-4 each have an activating effect on the alphaT-catenin promoter. Transfections with wild-type and mutant promoter constructs in cardiac HL-1 cells indicated that one GATA box is absolutely required for high alphaT-catenin promoter activity in these cells. Furthermore, we showed that the GATA-4 transcription factor specifically binds and activates the alphaT-catenin promoter in vivo in cardiac HL-1 cells. In vivo promoter analysis in transgenic mice revealed that the isolated alphaT-catenin promoter region could direct the tissue-specific expression of a LacZ reporter gene in concordance with endogenous alphaT-catenin expression.